Gab1 Acts as an Adapter Molecule Linking the Cytokine Receptor gp130 to ERK Mitogen-Activated Protein Kinase

• DOI: 10.1128/mcb.18.7.4109
• Publication Date: 2015-10-10T00:32:32Z
• Authors: Mariko Takahashi-...; Yuichi Yoshida; Toshiyuki Fukada; Takuya Ohtani; Yojiro Yamanaka; Keigo Nishida; Koichi Nakajima; Masahiko Hibi; Toshio Hirano
• Keywords: Glycoprotein 130; ROR1; Cyclin-dependent kinase 9

Gab1 has structural similarities with Drosophila DOS (daughter of sevenless), which is a substrate the protein tyrosine phosphatase Corkscrew. Both and have pleckstrin homology domain residues, potential binding sites for various SH2 domain-containing adapter molecules when they are phosphorylated. We found that was phosphorylated in response to cytokines, such as interleukin-6 (IL-6), IL-3, alpha interferon (IFN-α), IFN-γ. Upon stimulation IL-6 or form complex phosphatidylinositol (PI)-3 kinase SHP-2, homolog Mutational analysis gp130, common subunit family cytokine receptors, revealed neither residues gp130 nor its carboxy terminus required phosphorylation Gab1. Expression enhanced gp130-dependent mitogen-activated (MAP) ERK2 activation. A mutation 759, SHP-2 site abrogated interactions PI-3 well Furthermore, activation inhibited by dominant negative p85 kinase, wortmannin, Ras. These observations suggest acts an molecule transmitting signals ERK MAP receptor Ras involved Gab1-mediated