An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro

New insights into protein‐tyrosine kinase receptor signaling complexes

“…regions of sequence in their carboxy-termini to the SH3 domains of Grb-2 (Buday & Downward, 1993;Egan et al, 1993;Gale et al, 1993;Li et al, 1993;Olivier et al, 1993;Rozakis-Adcock et al, 1993;Simon et al, 1993). This is the first clear description of a physiological ligand for an SH3 domain.…”

Growth inhibition of breast cancer cells by Grb2 downregulation is correlated with inactivation of mitogen-activated protein kinase in EGFR, but not in ErbB2, cells

“…Loss of function mutations in the Drosophila and Caenorhabditis elegans homologues of GRB2 disrupt signaling by the Sevenless and Let-23 receptor tyrosine kinases, respectively, and the mutant phenotypes can be speci®cally rescued by expression of wildtype GRB2 (Clark et al, 1992;Simon et al, 1991Simon et al, , 1993Stern et al, 1993). Grb2 is critical for the transformation of ®broblasts by RTKs (Lowenstein et al, 1992;Pendergast et al, 1993;Xie et al, 1995), and for the proliferation of chronic myelogenous leukemic cells, which are regulated by the constitutively active Bcr-Abl tyrosine kinase (Tari et al, 1997).…”

Dominant effects of the bcr-abl oncogene on Drosophila morphogenesis

“…A potentially important binding site present in both P210 and P185 Bcr-Abl is tyrosine 177 which upon phosphorylation binds the mammalian SH3/SH2 adaptor protein, Grb2, to activate the Ras pathway during transformation (Pendergast et al, 1993;Puil et al, 1994). One scenario is that overexpression of Bcr-Abl in the developing eye competes with the Sevenless tyrosine kinase signal transduction pathway for the Drosophila Grb2 homolog, Drk and thus interferes with the di erentiation of photoreceptor cells (Olivier et al, 1993;Simon et al, 1993). Experiments are underway to test this hypothesis by looking at sev-GAL4 driven BcrAbl expression in animals heterozygous for deletion of drk and other components in the Sevenless signalling pathway.…”