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|Title:||c-Cbl is a negative regulator of GH-stimulated STAT5-mediated transcription|
|Authors:||Goh, E.L.K. |
|Citation:||Goh, E.L.K., Zhu, T., Leong, W.-Y., Lobie, P.E. (2002-09). c-Cbl is a negative regulator of GH-stimulated STAT5-mediated transcription. Endocrinology 143 (9) : 3590-3603. ScholarBank@NUS Repository. https://doi.org/10.1210/en.2002-220374|
|Abstract:||We have previously demonstrated that cellular stimulation with GH results in the formation of a multiprotein signaling complex. One component of this multiprotein signaling complex is the adapter molecule c-Cbl. Here we have examined the role of c-Cbl in the mechanism of GH signal transduction. Forced expression of c-Cbl in NIH3T3 cells did not alter GH-stimulated Janus kinase 2 tyrosine phosphorylation nor GH-stimulated p44/42 MAPK activation and consequent Elk-1-mediated transcription, c-Cbl overexpression did, however, result in enhanced and prolonged GH-stimulated activation of phosphatidylinositol 3-kinase. Forced expression of c-Cbl did not affect GH-stimulated STAT5 tyrosine phosphorylation, nuclear translocation, nor binding to DNA but markedly abrogated GH-stimulated STAT5-mediated transactivation. c-Cbl overexpression resulted in increased ubiquitination and proteosomal degradation of STAT5 and increased degradation of GH-stimulated tyrosine phosphorylated STAT5. Cellular pretreatment with the proteosomal inhibitor MG132 reversed the effect of c-Cbl overexpression with prolonged duration of GH-stimulated STAT5 tyrosine phosphorylation and restoration of STAT5-mediated transcription. Thus, c-Cbl is a negative regulator of GH-stimulated STAT5-mediated transcription by direction of STAT5 for proteosomal degradation.|
|Appears in Collections:||Staff Publications|
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