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

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.

author list (cited authors)
Feng, Q., Baird, D., Peng, X. u., Wang, J., Ly, T., Guan, J., & Cerione, R. A.
publication date
Springer Nature Publisher
published in
  • Neoplasms, Experimental
  • Animals
  • Oncogene Protein Pp60(v-src)
  • Receptor, Epidermal Growth Factor
  • Proto-Oncogene Proteins C-cbl
  • Cdc42 GTP-Binding Protein
  • Protein Binding
  • NIH 3T3 Cells
  • ErbB Receptors
  • Cell Proliferation
  • Cell Cycle Proteins
  • Mice
  • Mice, Nude
  • Phosphorylation
  • Phosphotyrosine
  • Transplantation, Heterologous
  • Guanine Nucleotide Exchange Factors
  • Cell Transformation, Neoplastic
  • Male
  • Rho Guanine Nucleotide Exchange Factors
  • Signal Transduction
  • Endocytosis
  • RNA Interference
  • Neoplasm Transplantation
citation count