Participation of both Gab1 and Gab2 in the activation of the ERK/MAPK pathway by epidermal growth factor

• DOI: 10.1042/bj20050229
• Publication Date: 2005-09-26T14:46:34Z
• Authors: Songshu Meng; Zhengming Chen; Teresita Munoz-An...; Jie Wu
• Keywords: 0301 basic medicine; Base Sequence; Epidermal Growth Factor; MAP Kinase Signaling System; Intracellular Signaling Peptides and Proteins; MAP Kinase Kinase 1; Down-Regulation; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Phosphoproteins; Gene Expression Regulation, Enzymologic; Enzyme Activation; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; COS Cells; Chlorocebus aethiops; Mutation; Animals; Humans; Gene Silencing; Extracellular Signal-Regulated MAP Kinases; Adaptor Proteins, Signal Transducing

Three members of Gab family docking proteins, Gab1, Gab2 and Gab3, have been identified in humans. Previous studies found that the hepatocyte growth factor preferentially utilizes Gab1 for signalling, whereas Bcr-Abl selectively signals through Gab2. Gab1–SHP2 interaction has shown to mediate ERK (extracellular-signal-regulated kinase) activation by EGF (epidermal factor). However, it was unclear whether signalling is dispensable cells where are co-expressed. Using T47D MCF-7 human breast carcinoma express endogenous Gab2, we examined role these proteins EGF-induced activation. It induced a similar amount SHP2–Gab1 SHP2–Gab2 complexes. Expression either SHP2-binding defective or mutant blocked Down-regulation siRNAs (small interfering RNAs) effectively inhibited EGF-stimulated pathway cell migration. Interestingly, inhibitory effect siRNA could be rescued not only expression an exogenous mouse but also vice versa, IRS1 (insulin receptor substrate 1). These results reveal plays pivotal can complement function pathway. Furthermore, critical threshold EGF.