α2 Integrin Subunit Cytoplasmic Domain-dependent Cellular Migration Requires p38 MAPK
2001
Abstract The α2 integrin subunit cytoplasmic domain uniquely supported epidermal growth factor (EGF)-stimulated migration on type I collagen. p38 MAP kinase- and phosphatidylinositol 3-kinase-specific inhibitors, but not a MEK-specific inhibitor, eliminated EGF-stimulated and unstimulated α2-cytoplasmic domain-dependent migration. Following adhesion to collagenous matrices, cells expressing the full-length α2 integrin subunit, but not cells expressing a chimeric α2 integrin subunit in which the α2-cytoplasmic domain was replaced by the cytoplasmic domain of the α1-subunit, exhibited sustained and robust phosphorylation of p38 MAP kinase. Expression of dominant negative p38 MAP kinase inhibited α2-cytoplasmic domain-dependent, EGF-stimulated migration as well as unstimulated migration on collagen. Expression of constitutively active Rac1(Val-12) augmented p38 MAP kinase activation and α2-cytoplasmic domain-dependent migration. It also rescued the ability of cells expressing the α1-cytoplasmic domain to activate p38 MAPK and to migrate. These results suggest that the α2 integrin cytoplasmic domain uniquely stimulates the p38 MAP kinase pathway that is required for unstimulated and EGF-stimulated migration on type I collagen.
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