Differential Role of β1Cand β1AIntegrin Cytoplasmic Variants in Modulating Focal Adhesion Kinase, Protein Kinase B/AKT, and Ras/Mitogen-activated Protein Kinase Pathways

• DOI: 10.1091/mbc.11.7.2235
• Publication Date: 2013-07-02T23:55:36Z
• Authors: Mara Fornaro; Craig A. Steger; Anton M. Bennett; J. Julie Wu; Lucia R. Languino
• Keywords: Integrin-linked kinase; PTK2

The integrin cytoplasmic domain modulates cell proliferation, adhesion, migration, and intracellular signaling. β 1 subunits, 1C 1A , that contain variant domains differentially affect proliferation; inhibits whereas promotes it. We investigated the ability of to modulate integrin-mediated signaling events proliferation survival in Chinese hamster ovary stable lines expressing either human or . different cytodomains did not association with endogenous α 2 V 5 subunits adhesion fibronectin TS2/16, a mAb Upon engagement exogenous integrins by fibronectin, cells showed significantly inhibited extracellular signal–regulated kinase (ERK) activation compared lines. In contrast, focal phosphorylation Protein Kinase B/AKT activity were affected. Selective exogenously expressed TS2/16 led stimulation but ERK2 activation; induced both proteins. show Ras was strongly reduced response expression constitutively active Ras, 61 (L), rescued -mediated down-regulation activation. Inhibition attributable an inhibitory effect on Ras/MAP pathway because activated MAPK antiproliferative effect. These findings variant, means unique mechanism, selectively MAP preventing without affecting signals stimulated cellular interactions matrix. highlight role for -specific cytodomain sequences maintaining balance signals.