Regulation of the Mitogen-activated Protein Kinase Signaling Pathway by SHP2

• DOI: 10.1074/jbc.m110547200
• Publication Date: 2002-07-26T14:49:43Z
• Authors: Jess M. Cunnick; Songshu Meng; Yuan Ren; Caroline Desponts; Hong-Gang Wang; Julie Y. Djeu; Jie Wu
• Keywords: ASK1

Gab1-SHP2 association is required for Erk mitogen-activated protein kinase activation by several growth factors. interaction activates SHP2. However, an activated SHP2 still needs to associate with Gab1 mediate activation. It was unclear whether dephosphorylate a negative phosphorylation site on or the pleckstrin homology (PH) domain target it plasma membrane. We found that expression of fusion consisting PH and active (Gab1PH-SHP2DeltaN) induced constitutive Mek1 Erk2 Linking SHP2DeltaN PDK1 FRS2beta myristoylation sequence also Gab1PH-SHP2DeltaN inhibited Src inhibitor Csk. Significantly, Ras, Gab1PH-SHP2DeltaN-induced blocked RasN17. These findings suggest signaling step upstream Ras. The tyrosine phosphatase activity essential function protein. Together, these data show sequence, besides binding sites, dispensable activation, suggesting primary role