Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.58092509
Two main functional regions have been defined in the cytoplasmic domain of the GH receptor by testing the activity of mutant forms of the receptor in several systems : Box 1 , a proline rich sequence in the membrane proximal part , is necessary for all GH effects and is probably the region of association with JAK 2 ; the C terminal region is required for the induction of specific genes . 0.58092509^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.82979658
We have recently shown that GH promotes the rapid association of GH receptor with the tyrosine kinase JAK 2 , activates JAK 2 , and promotes the tyrosyl phosphorylation of both JAK 2 and GH receptor . 0.82979658^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.50845768
The growth hormone receptor ( GHR ) is believed to interact predominantly with Jak 2 , but studies on cell lines have shown that it may also induce phosphorylation of Jak 1 and Jak 3 . 0.50845768^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.93934678
Constitutively phosphorylated JAK 2 , from COS 7 cells transiently transfected with murine JAK 2 cDNA , bound to SHC SH 2 GST fusion protein , demonstrating that the SHC SH 2 domain can bind tyrosyl phosphorylated JAK 2 in the absence of GHR . 0.93934678^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.57686695
We conclude : 1 ) kinase like domain deletion eliminates neither physical nor functional interaction between JAK 2 and the GHR ; 2 ) kinase domain deletion eliminates functional but not physical coupling of JAK 2 to the GHR ; 3 ) interaction with the GHR appears dependent on the NH 2 terminal one fifth of JAK 2 ; and 4 ) a GH responsive signaling unit can include as little as the GHR external and transmembrane domains and the JAK 2 kinase domain . . 0.57686695^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.64002857
These findings suggest that : 1 ) JAK 2 is required for GH dependent phosphorylation of Stats 1 , 3 , and 5 ; 2 ) tyrosines 333 and / or 338 are required for maximal tyrosyl phosphorylation of Stats 1 , 3 , and 5 ; 3 ) Stat 5 binds to a phosphorylated tyrosine ( s ) within amino acids 454 638 in addition to tyrosines 333 and / or 338 ; 4 ) GH stimulates tyrosyl phosphorylation of JAK 1 in addition to JAK 2 with JAK 2 having a much greater response ; 5 ) some Stat 3 and Stat 5 ( and possibly Stat 1 ) may bind to nonphosphorylated amino acids in GHR or to phosphorylated tyrosines in proteins that bind to GHR ( e . g . 0.64002857^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.53932671
Taken together , these results implicate association of GHR with JAK 2 and GH stimulated tyrosyl phosphorylation of an additional cellular protein in GH stimulated glucose transport and c fos and egr 1 expression . 0.53932671^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.75062875
Association of JAK 2 with the GHR is enhanced by receptor dimerization . 0.75062875^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :1.1704643
After receptor binding , growth hormone ( GH ) induces GH receptors ( GHR ) dimerization and JAK 2 is activated after its association with a dimerized GHR , stimulating the tyrosyl phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , IRS 2 and Shc proteins . 1.1704643^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Furthermore , dimerization of the GH receptor appears to be necessary for GH stimulated tyrosine phosphorylation of JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Expression of the human GH receptor in the mouse promyeloid , interleukin 3 dependent cell line , FDC P 1 , shows that this receptor can signal ligand dependent proliferation in these cells as well as induce the tyrosine phosphorylation of Jak 2 and the activation of transcription factors . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Dimerization of the GH receptor after ligand binding leads to the rapid association and tyrosine phosphorylation of the intracellular kinase , Jak 2 , as well as to the tyrosine phosphorylation and activation of STAT protein ( s ) . ^^^ A consistent pattern of proliferation , Jak 2 phosphorylation , and transcription factor activation was found for the 10 GH receptor mutants , a finding that is consistent with the hypothesis that the Jak STAT pathway is required for the signaling of proliferation in these cells . . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Although the receptor for growth hormone ( GH ) does not contain intrinsic tyrosine kinase activity , GH has recently been shown to promote the association of its receptor with JAK 2 tyrosine kinase , to activate JAK 2 , and to promote the tyrosyl phosphorylation of both GH receptor ( GHR ) and JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Following the growth hormone ( GH ) and GH receptor ( R ) interaction , the receptor and Janus tyrosine kinase 2 ( JAK 2 ) become tyrosine phosphorylated along with other intracellular proteins . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
These results define the importance of the membrane proximal 80 amino acids of the GH receptor ( with the conserved box 1 and box 2 domains ) with regard to GH activation of both Jak 2 and Stat ( s ) . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The biological effects of growth hormone ( GH ) are initiated by its binding to the GH receptor ( GHR ) followed by association and activation of the tyrosine kinase JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Growth hormone ( GH ) has recently been shown to activate the GH receptor ( GHR ) associated tyrosine kinase JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The proline rich region of the GH receptor is essential for JAK 2 phosphorylation , activation of cell proliferation , and gene transcription . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The binding of growth hormone ( GH ) to its receptor results in its dimerization followed by activation of Jak 2 kinase and tyrosine phosphorylation of the GH receptor itself , as well as Jak 2 and the transcription factors Stat 1 , 3 , and 5 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
For GH receptor ( GHR ) , both JAK 2 and the GHR undergo tyrosine phosphorylation upon GH stimulation . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Both JAK 1 and JAK 2 exhibit a nucleocytoplasmic distribution by immunocytochemistry in unstimulated serum deprived CHO cells stably transfected with rat GH receptor complementary DNA ( cDNA ) . ^^^ The nucleocytoplasmic localization of JAK 2 was verified by immunogold electron microscopy in both rat liver hepatocytes and CHO cells stably transfected with rat GH receptor cDNA . ^^^ No change in the nuclear content of JAK 1 or JAK 2 was observed upon ligand stimulation of GH receptor cDNA transfected cells with 100 nM human GH for 5 , 10 , 15 , 30 , or 60 min . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The GH receptor ( GHR ) is a member of the cytokine receptor superfamily ; its signaling involves the activation of Janus tyrosine kinases ( JAK 2 ) and Stat ( signal transducers and activators of transcription ) transcription factors . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Briefly , binding of GH to GH receptor induces receptor dimerization and activation of the tyrosine kinase JAK 2 . ^^^ Tyrosyl phosphorylation of GH receptor and JAK 2 recruits and activates signaling molecules such as Stat transcription factors , SHC , and insulin receptor substrates 1 and 2 that lead to the release of second messengers such as diacylglycerol , calcium , and nitric oxide and the activation of enzymes such as mitogen activated protein kinase , protein kinase C , phospholipase A 2 , and phosphatidylinositol 3 ' kinase . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Recent data suggest involvement of the Janus tyrosine kinase 2 ( JAK 2 ) in human GH induced tyrosine phosphorylation of the GH receptor and the insulin receptor substrates 1 and 2 ( IRS 1 and IRS 2 ) , leading to activation of the phosphatidylinositol 3 kinase and the acute insulin like effects in primary rat adipocytes . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Characterization of the mechanism of signaling utilized by GH indicated that tyrosine residues in GH receptor are not necessary for tyrosyl phosphorylation of IRS 2 ; however , the regions of GH receptor necessary for IRS 2 tyrosyl phosphorylation are the same as those required for JAK 2 association and tyrosyl phosphorylation . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
GH induced activation of JAK 2 , a GH receptor ( GHR ) associated tyrosine kinase , leads to tyrosine phosphorylation and activation of STATs ( signal transducers and activators of transcription ) 1 , 3 , and 5 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Finally , experiments performed with cells expressing wild type , truncated , or mutated forms of the GH receptor indicate that protein kinase Janus kinase 2 is involved in the GH dependent activation of the spi GAGA box . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
It has been previously demonstrated that growth hormone ( GH ) stimulated tyrosine phosphorylation of Jak 2 and Stat5a and Stat5b occurs in FDP C 1 cells expressing either the entire GH receptor or truncations of the cytoplasmic domain expressing only the membrane proximal 80 amino acids . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Stimulation of GH receptors leads to rapid activation of Jak 2 kinase and subsequent tyrosine phosphorylation of the GH receptor . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Growth hormone ( GH ) signaling requires activation of the GH receptor ( GHR ) associated tyrosine kinase , JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Continuous exposure to GH of BRL 4 cells , a rat hepatoma cell line stably transfected with rat GH receptor , induces a rapid but transient activation of Jak 2 and Stat 5 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Half of the carboxyl terminal region of the GH receptor is dispensable for FAK activation , but FAK activation does require the proline rich box 1 region of the GH receptor , indicative that FAK is downstream of JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
This review uses the GH receptor as a model system for studying cytokine signaling and summarizes some of the data used to establish JAK 2 as a GH receptor associated tyrosine kinase and to identify signaling molecules that lie downstream of JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Some of these phosphorylations are catalyzed by a GH receptor associated kinase identified as JAK 2 , a member of the Janus family of tyrosine kinases . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Growth hormone dependent tyrosine phosphorylation of a GH receptor associated high molecular WEIGHT protein immunologically related to JAK 2 . ^^^ A critical step in growth hormone ( GH ) signalling is the GH induced activation of the GH receptor ( GHR ) associated tyrosine kinase , JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Increased STAT5b DNA binding activity was observed in cells treated with the proteasome inhibitor MG 132 , suggesting that at least one component of the GH receptor ( GHR ) JAK 2 STAT5b signaling pathway becomes labile in response to continuous GH treatment . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
GH induces activation of the GH receptor ( GHR ) associated cytoplasmic tyrosine kinase , JAK 2 , resulting in tyrosine phosphorylation of the GHR and activation of STAT ( signal transducer and activator of transcription ) , Ras mitogen activated protein kinase , and phosphoinositol 3 kinase signaling pathways , among others . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
To confer GH responsiveness , C 6 cells were cotransfected with vectors that express the GH receptor ( pRc / CMV WTrGHR ) and Jak 2 ( pRc / CMV Jak 2 ) . ^^^ In summary , transient expression of the GH receptor and Jak 2 in C 6 cells creates a GH responsive system that activates STAT 1 , 3 , and 5 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The levels of the proteins which mediate GH receptor signaling ( STAT 1 , 3 , and 5 , and JAK 2 ) were quantified by Western blot analysis . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
SOCS 1 inhibited the tyrosine kinase activity of Janus kinase 2 ( JAK 2 ) directly , while SOCS 3 only inhibited JAK 2 when stimulated by the GH receptor . ^^^ These data suggest that SOCS 1 and 3 can suppress GH induced transcriptional activity , presumably by inhibiting the kinase activity of JAK 2 either directly in the case of SOCS 1 or via binding to the tyrosine phosphorylated GH receptor in the case of SOCS 3 . . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The finding of endotoxin inhibition of in vivo STAT 5 tyrosine phosphorylation in response to a supramaximal dose of GH in the absence of a change in GH receptor abundance or total GH stimulated JAK 2 tyrosine phosphorylation provides the first demonstration of acquired postreceptor GH resistance . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
In CHO cells stably expressing either the wild type ( wtGHR ) or a truncated form ( delta454GHR ) of the GH receptor in which GH induces a sustained activation of the receptor associated tyrosine kinase JAK 2 , we found that GH stimulation inhibited programmed cell death induced by withdrawal of survival factors . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
SOCS 1 , SOCS 2 , SOCS 3 , and CIS each strongly inhibited the GH receptor ( GHR ) dependent tyrosine phosphorylation of JAK 2 seen at low levels of transfected JAK 2 ; however , only SOCS 1 strongly inhibited the GHR independent tyrosine phosphorylation of JAK 2 seen at higher JAK 2 levels . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
This activation requires the proline rich box 1 region of the GH receptor required for JAK 2 association and is prevented by pretreatment of cells with the JAK 2 specific inhibitor AG 490 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
GH exerts its biological action by stimulating JAK 2 , a GH receptor ( GHR ) associated tyrosine kinase . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
GH binding to its receptor recruits and activates the receptor associated JAK 2 that in turn phosphorylates tyrosines within itself and the GH receptor . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The activated JAK 2 in turn phosphorylates tyrosines within itself and the associated GH receptor , forming high affinity binding sites for a variety of signaling molecules . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Interaction of GH with the cell surface GH receptor ( GHR ) causes activation of the GHR associated tyrosine kinase , JAK 2 , and consequent triggering of signaling cascades including the STAT , Ras / Raf / MEK1 / MAP kinase , and insulin receptor substrate 1 ( IRS 1 ) / PI3kinase pathways . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Mutation of the SHP 2 binding site in growth hormone ( GH ) receptor prolongs GH promoted tyrosyl phosphorylation of GH receptor , JAK 2 , and STAT5B . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Growth hormone ( GH ) inducible suppressors of cytokine signaling ( SOCS / CIS proteins ) inhibit GH receptor ( GHR ) signaling to STAT5b via phosphotyrosine dependent binding interactions with the tyrosine kinase JAK 2 ( SOCS 1 ) and / or the cytoplasmic tail of GHR ( CIS and SOCS 3 ) . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
In 1993 , GH receptor ( GHR ) was first observed to bind to the tyrosine kinase JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
We therefore tested the C2C12 myogenic cell line for its response to GH and demonstrate that C2C12 skeletal muscle cells rapidly respond to physiological levels of GH with increased tyrosine phosphorylation of the GH receptor , Janus kinase 2 , signal transducer and activator of transcription 5a and 5b , insulin receptor substrate 1 , and activation of MAPKs / ERKs and protein kinase B / Akt . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Interaction of GH with its cell surface GH receptor ( GHR ) , by virtue of receptor dimerization , causes activation of the GHR associated cytoplasmic tyrosine kinase , JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The effects of continuous high GH levels on GH signal transduction through the GH receptor ( GHR ) / Janus kinase 2 ( JAK 2 ) / signal transducer and activator of transcription 5 ( STAT 5 ) pathway as well as the desensitization of this pathway by suppressors of cytokine signaling ( SOCS ) were studied in transgenic mice overexpressing GHRH . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
GH signaling begins with activation of the GH receptor ( GHR ) associated cytoplasmic tyrosine kinase , Janus kinase 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
GH stimulates the phosphorylation of tyrosine residues in the GH receptor ( GHR ) , Janus kinase 2 ( JAK 2 ) , and other signaling proteins in a transient manner that subsides within 1 h . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Growth hormone ( GH ) promotes signaling by causing activation of the non receptor tyrosine kinase , JAK 2 , which associates with the GH receptor . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The ability of GH to stimulate lipogenesis and tyrosine phosphorylation of the GH receptor ( GHR ) , Janus kinase 2 ( Jak 2 ) , insulin receptor substrate 1 ( IRS 1 ) and 2 ( IRS 2 ) was greatly reduced in refractory as compared to responsive primary rat adipocytes . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
GH signaling depends on functional interaction of the GH receptor ( GHR ) and the cytoplasmic tyrosine kinase , Janus kinase 2 ( JAK 2 ) , which possesses a C terminal kinase domain , a catalytically inactive pseudokinase domain just N terminal to the kinase domain , and an N terminal half shown by us and others to harbor elements for GHR association . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The expression of MUP 2 is known to be stimulated by growth hormone ( GH ) , through the GH receptor ( GHR ) , Janus kinase 2 ( JAK 2 ) and signal transducer and activator of transcription 5 ( STAT 5 ) signal transduction pathway . ^^^ Aryl hydrocarbon receptor mediated suppression of GH receptor and Janus kinase 2 expression in mice . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
In these animals , GH receptor and membrane associated JAK 2 kinase are increased 4 . 5 and 6 fold , respectively . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
GH interacts with the GH receptor ( GHR ) , a cytokine superfamily receptor , to activate the cytoplasmic tyrosine kinase , Janus kinase 2 ( JAK 2 ) , and initiate intracellular signaling cascades . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
In liver , these responses were associated with increased abundance of the GH receptor protein ( GHR ; P < 0 . 05 ) , whereas the abundance of intracellular mediators of GH actions ( JAK 2 , STAT 5 , or STAT 3 ) remained unaffected . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
GH activated Janus associated kinase 2 ( JAK 2 ) signal transducers and activators of transcription 5 ( STAT 5 ) signaling was impaired in CRF rats , despite normal GH receptor ( GHR ) , JAK 2 , and STAT 5 protein levels . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Three features render the GH receptor unique : ( a ) an active ubiquitination system is required for both uptake ( endocytosis ) and degradation in the lysosomes ; ( b ) uptake of the receptor is a continuous process , independent of both GH binding and Jak 2 signal transduction ; ( c ) only the cell surface expression of dimerised GH receptors is controlled by the ubiquitin system . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Expression of the GH receptor may be reduced , although this is not a consistent finding , GH activation of the Janus kinase 2 signal transducer ( JAK 2 ) and activator of transcription ( STAT ) signal transduction pathway is depressed and this leads to reduced IGF 1 expression , and finally there is resistance to IGF 1 , a major mediator of GH action . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The insulin like effects are mediated by the cytosolic tyrosine kinase Janus kinase 2 ( JAK 2 ) upon GH GH receptor interaction , resulting in tyrosine phosphorylation of downstream targets including the GH receptor itself and insulin receptor substrate 1 ( IRS 1 ) and IRS 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Janus kinase 2 ( JAK 2 ) has been identified as the first intracellular step in GH receptor ( GHR ) signaling in many species , however , there is limited knowledge regarding the GH signaling pathway in the chicken . ^^^ Janus kinase 2 ( JAK 2 ) has been identified as the first intracellular step in GH receptor ( GHR ) signaling in many species , however , there is limited knowledge regarding the GH signaling pathway in the chicken . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Prop1df / Prop1df mice displayed unaltered GH receptor , JAK 2 and STAT5a / b protein levels . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Three key elements in this elucidation were the cloning of the GH receptor , the identification of Janus kinase ( JAK ) 2 as the receptor associated tyrosine kinase , and the delineation of signal transduction and activators of transcription ( STAT ) 5a / b as the key transcription factor ( s ) activated by JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
GH signals through the GH receptor ( GHR ) , a cytokine receptor superfamily member that couples to the cytoplasmic tyrosine kinase , Janus kinase 2 ( JAK 2 ) . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Total GH receptor ( GHR ) , JAK 2 , and STAT 5 signaling proteins and the time course of STAT 5 activation were also measured in liver after recombinant human GH administration by immunoblot and electrophoretic mobility shift analysis . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Thus STAT5b and HNF4alpha exhibit bi directional cross talk that may augment HNF4alpha dependent gene transcription while inhibiting STAT5b transcriptional activity via the inhibitory effects of HNF4alpha on JAK 2 phosphorylation , which leads to inhibition of STAT5b signalling initiated by the GH receptor at the cell surface . . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
At the tissue level , the action of GH is mediated by the GH receptor ( GHR ) and the receptor activated intracellular signaling pathway involving Janus kinase 2 ( JAK 2 ) and signal transducer and activator of transcription 5 ( STAT 5 ) . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Insulin restored the ability of a second GH exposure to induce phosphorylation of MEK1 / 2 and ERK1 / 2 without altering GH receptor levels or GH induced phosphorylation / activation of JAK 2 and Raf 1 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Distinct cytoplasmic regions of the growth hormone receptor are required for activation of JAK 2 , mitogen activated protein kinase , and transcription . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Interaction of the growth hormone receptor cytoplasmic domain with the JAK 2 tyrosine kinase . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Identification of JAK 2 as a growth hormone receptor associated tyrosine kinase . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Further analysis revealed that growth hormone receptor and JAK 2 kinase phosphorylation as well as mitogen activated protein ( MAP ) kinase activity were significantly lower in old animals compared to the adult or middle age groups ( p < . 05 ) . ^^^ Old caloric restricted animals demonstrated a significant increase in growth hormone receptor and JAK 2 kinase phosphorylation and MAP kinase activity in response to growth hormone . ^^^ The results demonstrate that growth hormone increases growth hormone receptor and JAK 2 kinase phosphorylation as well as MAP kinase activity in liver . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Jak 2 and STAT 1 colocalized in the proximal ends of presecretory and secretory stage ameloblasts , supporting work by others that growth hormone receptor is located at that site . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Identification of growth hormone receptor ( GHR ) tyrosine residues required for GHR phosphorylation and JAK 2 and STAT 5 activation . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The growth hormone receptor associates with Jak 1 , Jak 2 and Tyk 2 in human liver . ^^^ Studies in cell lines have shown that Jak 2 is the primary tyrosine kinase involved in signal transduction by the growth hormone receptor ( GHR ) . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The growth hormone receptor ( GHR ) , a cytokine receptor superfamily member , requires the JAK 2 tyrosine kinase for signaling . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Specific cytoplasmic domains of the growth hormone receptor mediate Jak 2 activation , metabolic actions of growth hormone , Stat activation , and calcium influx . . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Growth hormone receptor ubiquitination , endocytosis , and degradation are independent of signal transduction via Janus kinase 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Subcellular trafficking of growth hormone receptor and Jak 2 under ligand exposure . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Using mouse embryonic fibroblasts derived from Jak 2 null embryos and their wildtype littermate controls , we demonstrated that Jak 2 deficiency decouples growth hormone receptor signaling from its downstream mediators , the signal transducer and activator of transcription ( Stat ) 5a and 5b . . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Growth hormone receptor , JAK 2 , STAT5a , and STAT5b protein levels were unaltered in CRF . ^^^ Growth hormone induced JAK 2 , growth hormone receptor ( GHR ) , and STAT 5 tyrosine phosphorylation was significantly depressed in CRF as was nuclear translocation of phosphorylated STAT 5 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Growth hormone receptor ( GHR ) is a cytokine receptor superfamily member that binds growth hormone ( GH ) via its extracellular domain and signals via interaction of its cytoplasmic domain with JAK 2 and other signaling molecules . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Janus kinase 2 enhances the stability of the mature growth hormone receptor . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Growth hormone is believed to activate the growth hormone receptor ( GHR ) by dimerizing two identical receptor subunits , leading to activation of JAK 2 kinase associated with the cytoplasmic domain . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Although GHR in both cells was expressed at similar abundance , dimerized normally and caused JAK 2 activation in response to GH independent of TACE expression , PMA was unable to generate GHBP from Null / R cells . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Each receptor mediated a dose dependent activation of STAT 1 and STAT 3 , and for IL 3R and GHR this process was enhanced by JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
GH induced JAK 2 kinase and GHR complex phosphorylation as well as MAP kinase activity were significantly lower in 31 month old animals than in either the 10 or 17 month old groups ( P < 0 . 05 ) . ^^^ The results of this study demonstrate that GH induces phosphorylation of JAK 2 and the GHR complex , activates MAP kinase , and increases the expression of IGF 1 messenger RNA in liver . ^^^ By 31 months , there was a decrease in IGF 1 gene expression that was associated with a marked decline in JAK 2 and GHR complex phosphorylation . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
JAK 2 has been identified to be a GHR associated tyrosine kinase . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
This region of GHR is required for GH dependent JAK 2 association and activation ( VanderKuur , J . ^^^ The correlation between JAK 2 tyrosyl phosphorylation and IRS 1 tyrosyl phosphorylation in response to GH , interferon gamma , and leukemia inhibitory factor and in cells expressing different GHR mutants , provides evidence that IRS 1 may interact with JAK 2 or an auxiliary molecule that binds to JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The binding of growth hormone ( GH ) to its receptor ( GHR ) activates JAK 2 and STATs as well as ERK / MAP kinases . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
JAK 2 has been identified as a tyrosine kinase associated with GHR and other receptors of the superfamily . ^^^ Binding of GH to its receptor results in dimerization of the GHR , phosphorylation of JAK 2 and of the GHR . ^^^ The C terminal region of the GHR is required for tyrosine phosphorylation of the receptor and for a hormonal effect on gene transcription , whereas only 46 membrane proximal amino acids of the cytoplasmic domain are necessary for activation of JAK 2 and transduction of the GH proliferative signal . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
DEX and PMA also decrease GH induced tyrosyl phosphorylation of GHR and JAK 2 with a magnitude and time course correlating with that of inhibition of GH binding . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The model presented is one in which GH binding to two GHRs causes dimerization of GHR , activation of the GHR associated JAK 2 tyrosine kinase , and tyrosyl phosphorylation of both JAK 2 and GHR . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Neither tyrosine phosphorylation of GHR nor of Jak 2 was inhibited at the nonpermissive temperature . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Finally , GHR 05 treatment of IM 9 cells , a human cell line expressing a functional human GHR , leads to cell proliferation mediated by the generation of GH specific signals , including phosphorylation of the JAK 2 tyrosine kinase and activation of STAT5 . . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
To dissect further the mechanism by which GH activates Stat5A and B , the requirement for JAK 2 in GH dependent Stat 5 tyrosyl phosphorylation was assessed using JAK 2 deficient cells expressing GHR ( gamma2A GHR ) and the wild type parental cell line expressing GHR ( 2C4 GHR ) . ^^^ GH induced tyrosyl phosphorylation of Stat5B in 2C4 GHR cells but not in the JAK 2 deficient , gamma2A GHR cells , indicating that JAK 2 is required for GH dependent tyrosyl phosphorylation of Stat5B . ^^^ Taken together , these findings suggest that : 1 ) GH activates both Stat5A and Stat5B in several cell types ; 2 ) the pattern of bands observed differs for Stat5A and Stat5B ; 3 ) GH dependent tyrosyl phosphorylation of Stat5A requires specific regions of GHR , and these requirements are the same as for Stat5B ; and 4 ) JAK 2 kinase is required for GH dependent tyrosyl phosphorylation of Stat5B and , most likely , Stat5A . . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The dimerization of GHRs leads to the activation of Janus kinase 2 ( JAK 2 ) , a nonreceptor tyrosine kinase that associates with the cytoplasmic domain of GHR . ^^^ It is thought that all signaling downstream from GHR depends on this initial activation of JAK 2 . ^^^ Once activated , JAK 2 tyrosyl phosphorylates both itself and the cytoplasmic domain of GHR . ^^^ The signaling molecules that are recruited and activated by the GHR JAK 2 complex include signal transducers and activators of transcription ( Stat ) factors , the adapter protein Shc , and the insulin receptor substrates ( IRSs ) 1 and 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Mutant GH was less potent than wild type GH not only in phosphorylation of tyrosine residues in GHR , janus kinase 2 ( JAK 2 ) , and signal transducers and activators of transcription 5 ( STAT 5 ) in IM 9 cells , but also in metabolic responses of BaF / GM cells , a stable clone transfected with cDNA of the chimera of the extracellular domain of human GHR , the transmembrane and the cytoplasmic domain of the human thrombopoietin receptor . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Co transfections in 293 cells further show that Grb 10 interacts with both the GHR and Jak 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
In summary , continuous insulin treatment in rat H 4 hepatoma cells reduces GH binding , immunoreactive GHR , GH induced phosphorylation of JAK 2 , and GH induced tyrosine phosphorylation of STAT5B . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Dimerization of the GHR activates phosphorylation cascades involving MAP kinases and the Janus kinase , JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Thus , forced dimerization of the transmembrane and cytoplasmic domains of the GHR in the absence of the extracellular domain can lead to the constitutive activation of known GH signaling end points , supporting the view that proximity of Janus kinase 2 ( JAK 2 ) kinases is the essential element in signaling . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Our results demonstrate that ( 1 ) both GHR mRNA and GHR immunoreactivity are present in HL 60 cells ; ( 2 ) GH treatment results in an increase in the phosphorylation of the GHR associated Jak 2 and Stat 3 proteins , indicating the ability of the hormone to induce receptor activation ; and ( 3 ) activation of GHR increases the activity of Akt , a serine / threonine kinase that plays a prominent role in the regulation of cell survival . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Here , we present evidence that the proteasomal inhibitor MG 132 prolongs the GH induced activity of both GHR and JAK 2 , presumably through stabilization of GHR and JAK 2 tyrosine phosphorylation . ^^^ Experiments with a GHR truncated tail mutant ( GHR ( 1 369 ) ) led to a prolonged JAK 2 phosphorylation caused by the loss of a phosphatase binding site . ^^^ GHR complexes before and after endocytosis showed that JAK 2 as well as other activated proteins are bound to the GHR not only at the cell surface but also intracellularly , suggesting that the GHR signal transduction continues in endosomes . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The interaction of GH with GH receptors ( GHR ) on target cells promotes the association of the cellular tyrosine kinase JAK 2 with the GHR , initiating tyrosine phosphorylation of GHR and JAK 2 , and activation of multiple signaling cascades . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
GH binding to the GHR results in the formation of a GH ( GHR ) ( 2 ) complex and the initiation of signal transduction cascades via the activation of the tyrosine kinase JAK 2 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Further , we determined that PMA pretreatment desensitized a cleavage sensitive GHR mutant , but not a cleavage insensitive mutant , to GH induced JAK 2 activation . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Activation of the GHR signal transduction pathway begins with attachment of two Janus kinase 2 ( JAK 2 ) molecules to the intracellular domains of the GHRs leading to phosphorylation of the tyrosine residues of JAK 2 and the GHRs ; thereafter the signal transduction and activators of transcription ( STAT ) and Ras mitogen activated protein kinase pathways are enhanced . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
In C2C12 ( GHR ) cells , we observed an increased activation of the Janus kinase 2 ( Jak 2 ) , signal transducers and activator of transcription 5 ( Stat 5 ) , mitogen activated protein kinase ( MAPK ) and protein kinase B ( Akt ) upon acute GH stimulation . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Thus , we conclude that activation of JAK 2 kinase and the subsequent tyrosine phosphorylation is not required for nuclear translocation of GH but is pivotal for the removal of the hormone from the nucleus , and that GH translocates into the nucleus in a GHR dimerized dependent fashion . . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The effect of heterodimerization was studied by comparing activation of Janus kinase 2 , signal transducer and activator of transcription ( STAT ) 1 , STAT 3 , STAT 5 , and MAPK in Chinese hamster ovary cells stably transfected with chimeric genes encoding receptors consisting of cytosolic and transmembrane parts of oGHR and oPRLR , extracellular domains of human granulocyte and macrophage colony stimulating factor ( hGM CSF ) receptor alpha or beta , and cells transfected with the two forms ( alpha or beta ) of PRLR and GHR . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Since GH regulates cellular cytoskeleton with potential implications in GH signaling , we investigated the effects of actin cytoskeleton disruption on the kinetics of GH activated GHR / Janus kinase 2 ( JAK 2 ) / signal transducer and activator of transcription 5 ( STAT 5 ) signaling pathway . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
The resultant GHR is truncated at amino acid 449 ( GHR 1 449 ) after Box 1 , the Janus kinase 2 binding domain of the receptor . ^^^ Western blot analysis showed GH induced phosphorylation of Janus kinase 2 , signal transducer and activator of transcription ( Stat ) 3 , and Erk 2 for both GHR 1 449 and wild type GHR . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
GHR signaling is transduced via the receptor associated cytoplasmic tyrosine kinase called Janus protein kinase 2 ( JAK 2 ) . ^^^ JAK 2 was also represented in the CM fraction , but was less enriched ( 2 . 5 fold ) than GHR . ^^^ Correspondingly , GH induced tyrosine phosphorylated GHR , JAK 2 , and ERK1 / 2 were highly represented in the CM fraction , whereas tyrosine phosphorylated STAT 5 was enriched in the non membranous fraction of the post nuclear supernatant . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Furthermore , GH induced rapid , time and dose dependent signaling events in LNCaP cells , including phosphorylation of JAK 2 tyrosine kinase , of GHR itself and of STAT5A ( JAK 2 STAT5A pathway ) , of p42 / p44 MAPK and of Akt / PKB . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
In signaling experiments , brief pretreatment of GH responsive human fibrosarcoma cells with anti GHR ( ext mAb ) dramatically inhibited GH induced Janus kinase 2 and signal transducer and activator of transcription 5 tyrosine phosphorylation and prevented GH induced GHR disulfide linkage ( a reflection of GH induced conformational changes ) . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Incubation of cells with IL 1beta ( 10 ng / ml , 24 h ) had no effect on the relative abundance of GHR or signaling proteins JAK 2 , STAT5b , and ERK1 / 2 in cell lysates . ^^^ Baseline phosphorylation of GHR , JAK 2 , STAT5b , and ERK1 / 2 was minimal . ^^^ After GH stimulation , tyrosine phosphorylation of GHR , JAK 2 , STAT5b , and ERK1 / 2 increased 2 to 10 fold . ^^^ However , neither the time course nor the magnitude of GHR , JAK 2 , and ERK1 / 2 phosphorylation by GH were significantly altered by IL 1 . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
Western blot analysis showed GH induced phosphorylation of Jak 2 and Stat 5 for both GHR 1 656 and GHRwt , although reduced Stat 5 activity was detected with GHR 1 656 , consistent with lower levels of expression of GHR 1 656 than GHRwt at the cell surface . ^^^
Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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Interacting proteins: P10912 and O60674	Pubmed	SVM Score :0.0
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