GAREM, a novel adaptor protein for growth factor receptor-bound protein 2, contributes to cellular transformation through the activation of extracellular signal-regulated kinase signaling.

Article Details

Citation

Tashiro K, Tsunematsu T, Okubo H, Ohta T, Sano E, Yamauchi E, Taniguchi H, Konishi H

GAREM, a novel adaptor protein for growth factor receptor-bound protein 2, contributes to cellular transformation through the activation of extracellular signal-regulated kinase signaling.

J Biol Chem. 2009 Jul 24;284(30):20206-14. doi: 10.1074/jbc.M109.021139. Epub 2009 Jun 9.

PubMed ID
19509291 [ View in PubMed
]
Abstract

Adaptor proteins for the various growth factor receptors play a crucial role in signal transduction through tyrosine phosphorylation. Several candidates for adaptor proteins with potential effects on the epidermal growth factor (EGF) receptor-mediated signaling pathway have been identified by recent phosphoproteomic studies. Here, we focus on a novel protein, GAREM (Grb2-associated and regulator of Erk/MAPK) as a downstream molecule of the EGF receptor. GAREM is phosphorylated at tyrosine 105 and 453 after EGF stimulation. Grb2 was identified as its binding partner, and the proline-rich motifs of GAREM are recognized by the N- and C-terminal SH3 domains of Grb2. In addition, the tyrosine phosphorylations of GAREM are necessary for its binding to Grb2. Because the amino acid sequence surrounding tyrosine 453 is similar to the immunoreceptor tyrosine-based inhibitory motif, Shp2, a positive regulator of Erk, binds to GAREM in this phosphorylation-dependent manner. Consequently, Erk activation in response to EGF stimulation is regulated by the expression of GAREM in COS-7 and HeLa cells, which occurs independent of the presence of other binding proteins, such as Gab1 and SOS, to the activated EGF receptor. Furthermore, the expression of GAREM has an effect on the transformation activity of cultured cells. Together, these findings suggest that GAREM plays a key role in the ligand-mediated signaling pathway of the EGF receptor and the tumorigenesis of cells.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Epidermal growth factor receptorP00533Details
Growth factor receptor-bound protein 2P62993Details
Tyrosine-protein phosphatase non-receptor type 11Q06124Details