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


  • 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.

published proceedings

  • Nat Cell Biol

author list (cited authors)

  • Feng, Q., Baird, D., Peng, X. u., Wang, J., Ly, T., Guan, J., & Cerione, R. A.

citation count

  • 102

complete list of authors

  • Feng, Qiyu||Baird, Dan||Peng, Xu||Wang, Jianbin||Ly, Thi||Guan, Jun-Lin||Cerione, Richard A

publication date

  • January 2006