Activated Cdc42 sequesters c-Cbl and prevents EGF receptor degradation.
Cdc42 is a Ras-related protein that has been implicated in the control of normal cell growth, and when improperly regulated, in cellular transformation and invasiveness. A variety of extracellular stimuli, including epidermal growth factor (EGF), activate Cdc42. Here, we show that activation of Cdc42 protects the EGF receptor from the negative regulatory activity of the c-Cbl ubiquitin ligase. Activated Cdc42 binds to p85Cool-1 (for cloned-out-of-library)/beta-Pix (for Pak-interactive exchange factor), a protein that directly associates with c-Cbl. This inhibits the binding of Cbl by the EGF receptor and thus prevents Cbl from catalyzing receptor ubiquitination. The role played by Cdc42 in regulating the timing of EGF receptor-Cbl interactions is underscored by the fact that constitutively active Cdc42(F28L), by persistently blocking the binding of Cbl to these receptors, leads to their aberrant accumulation and sustained EGF- stimulated ERK activation, thus resulting in cellular transformation.[1]References
- Activated Cdc42 sequesters c-Cbl and prevents EGF receptor degradation. Wu, W.J., Tu, S., Cerione, R.A. Cell (2003) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg