| Interacting proteins: O43597 and P22681 |
Pubmed |
SVM Score :1.0835265 |
| Here , we demonstrate that hSPRY 2 associates directly with c Cbl , a known down regulator of RTK signaling . 1.0835265^^^ |
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| Interacting proteins: O43597 and P22681 |
Pubmed |
SVM Score :0.88014708 |
| It has been shown that hSpry 2 interacts directly with c Cbl , an E 3 ubiquitin ligase , which promotes the downregulation of receptor tyrosine kinases ( RTKs ) . 0.88014708^^^ Our results indicate that the interaction of hSpry 2 with c Cbl might serve as a mechanism for the downregulation of hSpry 2 during receptor tyrosine kinase signaling . . 0.65639^^^ |
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| Interacting proteins: O43597 and P22681 |
Pubmed |
SVM Score :0.0 |
| Current evidence indicates that Cbl is a key protein that interacts directly with Spry 2 following activation of receptor tyrosine kinases ( RTKs ) . ^^^ It appears to be the ability of Cbl to interact as an E 3 ubiquitin ligase on specific target proteins and as a docking protein in other contexts that dictates the differential effects Spry 2 has on the Ras / MAP kinase pathway following EGFR and FGFR activation . . ^^^ |
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| Interacting proteins: O43597 and P22681 |
Pubmed |
SVM Score :0.0 |
| Evidence is presented herein that describes the functional implications of the direct association between human Sprouty 2 ( hSpry 2 ) and c Cbl , and its impact on the cellular localization and signalling capacity of EGFR . ^^^ Correlative evidence showed the failure of hSpry2DeltaN11 and mSpry 4 , both deficient in c Cbl binding , to instigate these effects . hSpry 2 interacts specifically with the c Cbl RING finger domain and displaces UbcH 7 from its binding site on the E 3 ligase . ^^^ We conclude that hSpry 2 potentiates EGFR signalling by specifically intercepting c Cbl mediated effects on receptor down regulation . . ^^^ |
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| Interacting proteins: O43597 and P22681 |
Pubmed |
SVM Score :0.0 |
| In this study it is demonstrated that hSpry 2 is tyrosine phosphorylated upon stimulation by either FGFR or EGF and subsequently binds endogenous c Cbl with high affinity . ^^^ A conserved motif on hSpry 2 , together with phosphorylation on tyrosine 55 , is required for its enhanced interaction with the SH 2 like domain of c Cbl . ^^^ A hSpry 2 mutant ( Y55F ) that did not exhibit an enhanced binding with c Cbl failed to retain EGF receptors on the cell surface . ^^^ Furthermore , individually mutating hSpry 2 residues 52 59 to alanine indicated a tight correlation between their affinity for c Cbl binding and their inhibition of ERK 2 activity in the FGFR pathway . ^^^ We postulate that tyrosine phosphorylation `` activates ' ' hSpry 2 by enhancing its interaction with c Cbl and that this interaction is critical for its physiological function in a signal specific context . . ^^^ |
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| Interacting proteins: O43597 and P22681 |
Pubmed |
SVM Score :0.0 |
| Previous studies have shown that growth factor stimulation induces the proteolytic degradation of hSpry 2 by stimulating tyrosine phosphorylation on hSpry 2 , which in turn promotes c Cbl binding and polyubiquitination . ^^^ A mutant of hSpry 2 that is deficient in serine phosphorylation displays enhanced tyrosine phosphorylation and c Cbl binding , indicating that serine phosphorylation stabilizes hSpry 2 by exerting an antagonistic effect on tyrosine phosphorylation . ^^^ |
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| Interacting proteins: O43597 and P22681 |
Pubmed |
SVM Score :0.0 |
| Human Sprouty 2 ( hSpry 2 ) binds the catalytic RING Finger of Casitas B lineage lymphoma ( c Cbl ) , an E 3 ubiquitin ligase that has been identified to target EGFR degradation . ^^^ Overexpressed hSpry 2 induces a prolonged EGFR mediated MAP kinase activation . hSpry 2 acts to sequester c Cbl molecules from activated EGFR and impedes EGFR ubiquitination and downregulation , thereby potentiating the amplitude and longevity of intracellular signals . ^^^ |
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| Interacting proteins: O43597 and P22681 |
Pubmed |
SVM Score :0.0 |
| NA |
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