Cool-1 functions as an essential regulatory node for EGFreceptor- and Src-mediated cell growth

• Qiyu Feng ^[1] ; Dan Baird ^[1] ; Richard A. Cerione ^[1]
  1. [1] Cornell University

     Cornell University

     City of Ithaca, Estados Unidos

     
• Localización: Nature: Cell biology, ISSN 1465-7392, Nº. 9, 2006, págs. 945-956
• Idioma: inglés
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• Resumen

  • Cool-1 (cloned-out of library 1) has a key role in regulating epidermal growth factor receptor (EGFR) degradation. Here, we show that Cool-1 performs this function by functioning as both an upstream activator and downstream target for Cdc42. EGF-dependent phosphorylation of Cool–1 enables it to act as a nucleotide exchange factor for Cdc42 and to form a complex with the E3 ligase Cbl, thus regulating Cbl-catalysed EGFR degradation. The EGF-dependent phosphorylation is normally transient; however, Cool-1 phosphorylation is sustained in cells expressing v–Src and is essential for cellular transformation, as well as for v-Src-induced tumour formation in mice. These findings demonstrate that the regulated phosphorylation of Cool-1 is necessary to maintain the balance between normal signalling by EGFR and Src versus aberrant growth and transformation.