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Nat Cell Biol. 2006 Sep;8(9):945-56. Epub 2006 Aug 6.

Cool-1 functions as an essential regulatory node for EGF receptor- and Src-mediated cell growth.

Author information

1
Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA.

Abstract

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.

Comment in

PMID:
16892055
DOI:
10.1038/ncb1453
[Indexed for MEDLINE]

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