| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.67436277 |
| Since coexpression of c Cbl with wild type APS , but not C terminal truncated APS , synergistically inhibited PDGF induced c fos promoter activation , c Cbl could be a mechanism of inhibitory action of APS on PDGF receptor signaling . . 0.67436277^^^ In vitro and in vivo binding experiments indicate that the tyrosine phosphorylated C terminal region of APS bound to c Cbl , which has been shown to be a negative regulator of tyrosine kinases . 0.60532864^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :1.4944216 |
| Here , we report that APS was tyrosine phosphorylated by Janus kinase 2 ( JAK 2 ) at its C terminal tyrosine residue and interacted with c Cbl . 1.4944216^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.67696442 |
| In insulin stimulated 3T3 L 1 adipocytes , APS co precipitated with phosphorylated c Cbl . 0.67696442^^^ T APS cells overexpressing the insulin receptor and APS , APS co precipitated with c Cbl but not in CHO . 0.55318908^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.0 |
| APS couples c Cbl to the insulin receptor , resulting in ubiquitination of the insulin receptor . ^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.0 |
| Most importantly , the Cbl mediated transcription initiation at the ssu promoter in vitro is abolished in the presence of an early metabolite of the sulphate assimilatory pathway , adenosine 5 ' phosphosulphate ( APS ) . ^^^ Our data comprise the first evidence that APS may act as the negative cofactor of the transcriptional regulator Cbl , and that APS , and not sulphate itself , serves as the signalling molecule for sulphate excess . . ^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.0 |
| The adapter protein APS has previously been shown to be involved in recruiting the ubiquitin E 3 ligase c Cbl to the insulin receptor , the platelet derived growth factor beta receptor and the erythropoietin receptor , leading to increased degradation of the receptors and inhibition of mitogenesis . ^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.0 |
| We previously showed [ Ahmed , Smith and Pillay , FEBS Lett . 475 , 31 34 ] , for the first time , that insulin stimulated phosphorylation of APS led to interaction with c Cbl in 3T3 L 1 adipocytes and in transfected Chinese hamster ovary ( CHO ) cells . ^^^ We therefore conclude that , despite the ability to couple to c Cbl , APS functions as a positive regulator of IR signalling and , although SH 2 B is a poor substrate for the IR , its association with the IR allows it to regulate pathways downstream of the receptor independently of its phosphorylation . . ^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.0 |
| Ectopic expression of APS facilitated insulin stimulated phosphorylation of tyrosines 665 and 709 in Cbl b . ^^^ The phosphorylation of APS produced by insulin drove the translocation of both c Cbl and Cbl b to the plasma membrane . ^^^ A Cbl mutant incapable of dimerization failed to interact with APS and to undergo tyrosine phosphorylation in response to insulin , indicating an essential role of Cbl dimerization in these processes . ^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.0 |
| The adaptor protein APS is a substrate of the insulin receptor and couples receptor activation with phosphorylation of Cbl to facilitate glucose uptake . ^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.0 |
| Primary and essential role of the adaptor protein APS for recruitment of both c Cbl and its associated protein CAP in insulin signaling . ^^^ Although both APS and CAP ( c Cbl associated protein ) interact with c Cbl during insulin signaling , the relative importance of each protein in recruiting c Cbl has not been clear . ^^^ In cells co expressing insulin receptor and CAP , without APS , no association of the insulin receptor and CAP could be detected and no insulin stimulated phosphorylation of Cbl was observed . ^^^ Insulin stimulated Cbl phosphorylation was reconstituted when APS was co expressed with insulin receptor , with or without CAP . ^^^ In 3T3 L 1 adipocytes , small interfering RNA mediated knockdown of the mouse APS gene abolished the insulin stimulated phosphorylation of c Cbl . ^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.0 |
| The APS adapter protein plays a pivotal role in coupling the insulin receptor to CAP and c Cbl in the phosphatidylinositol 3 kinase independent pathway of insulin stimulated glucose transport . ^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.0 |
| It has been postulated that adenosine 5 phosphosulfate ( APS ) is responsible for abolishing Cbl activated transcription from the ssu promoter ( Bykowski et al . , 2002 ) . ^^^ To elucidate the structural basis of Cbl function and to confirm the role of APS as an anti inducer , the cofactor binding domain of Cbl ( c Cbl , MW = 26 kDa ) was cloned , purified and crystallized in the presence of APS . ^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.0 |
| In spite of these differences , both FL Grb 10 and the BPS SH 2 fragment inhibited insulin stimulated phosphorylation of IRS 1 , IRS 2 , Akt / PKB , Shc , ERK1 / 2 , APS , and c Cbl to a similar extent . ^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.0 |
| Structural characterization of a novel Cbl phosphotyrosine recognition motif in the APS family of adapter proteins . ^^^ Cbl is recruited to and phosphorylated by the insulin receptor in adipose cells through the adapter protein APS . ^^^ APS is phosphorylated by the insulin receptor on a C terminal tyrosine residue , which then serves as a binding site for the Cbl TKB domain . ^^^ Using 10 ray crystallography , site directed mutagenesis , and calorimetric studies , we have characterized the interaction between the Cbl TKB domain and the Cbl recruitment site in APS , which contains a sequence motif , RA ( V / I ) XNQpY ( S / T ) , that is conserved in the related adapter proteins SH 2 B and Lnk . ^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.0 |
| The APS adapter protein is recruited to the autophosphorylated kinase domain of the insulin receptor and initiates the phosphatidylinositol 3 kinase ( PI3K ) independent pathway of insulin stimulated glucose transport by recruiting CAP and c Cbl . ^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.0 |
| Tyrosine phosphorylation of APS leads to recruitment of c Cbl and Crk , while overexpression of APS mutant inhibits GLUT 4 translocation in response to insulin , but the regulation of APS expression in skeletal muscle has not been previously reported . ^^^ |
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| Interacting proteins: O14492 and P22681 |
Pubmed |
SVM Score :0.0 |
| In plasma membrane fractions , neither the high fat diet nor insulin altered the insulin receptor beta subunit ( IR beta ) , APS ( adaptor protein containing PH and SH 2 domains ) , c Cbl , or TC 10 protein concentration , but high fat feeding did decrease CAP protein concentration . ^^^ APS , c Cbl , CAP , and TC 10 messenger RNA were present in the skeletal muscle and reflected the protein concentration of experimental groups . ^^^ Despite insulin stimulated plasma membrane IR beta tyrosine phosphorylation being unaffected by high fat feeding , c Cbl tyrosine phosphorylation , the kinase activity of IR beta toward APS , and glucose transporter 4 protein concentration were all significantly reduced in insulin stimulated plasma membrane prepared from the skeletal muscle of high fat fed animals . ^^^ |
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