Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors

We previously found that the adapter protein Gab1 (110 kD) is tyrosine-phos phorylated and forms a complex with SHP-2 and PI-3 kinase upon stimulation through either the interleukin-3 receptor (IL-3R) or gp130. the common rece ptor subunit of IL-6-family cytokines. In this report, we identified anothe r adapter molecule (100 kD) interacting with SHP-2 and PI-3 kinase in respo nse to various stimuli. The molecule displays striking homology to Gab1 at the amino acid level; thus, we named it Gab2. It contains a PH domain, prol ine-rich sequences, and tyrosine residues that bind to SH2 domains when the y are phosphorylated. Gab1 is phosphorylated on tyrosine upon stimulation t hrough the thrombopoietin receptor (TPOR), stem cell factor receptor (SCFR) , and T-cell and B-cell antigen receptors (TCR and BCR, respectively), in a ddition to IL-3R and gp130. Tyrosine phosphorylation of Gab2 was induced by stimulation through gp130, IL-2R, IL-3R, TPOR. SCFR, and TCR. Gab1 and Gab 2 were shown to be substrates for SHP-2 in vitro. Overexpression of Gab2 en hanced the gp130 or Src-related kinase-mediated ERK2 activation as that of Gab1 did. These data indicate that Gab-family molecules act as adapters for transmitting various signals. (C) 1999 by The American Society of Hematolo gy.