AN INWARD RECTIFIER K-CELLS THE TYROSINE PHOSPHORYLATION OF THE PP125(FAK) AND ASSOCIATED PROTEINS - ROLE IN NEURITOGENESIS( CURRENT MODULATES IN NEUROBLASTOMA)

The relationships between the integrin-mediated activation of inward r ectifyier K+ channels (K-IR), the phosphorylation of pp125(FAK) and th e rescue of neuritogenesis were studied in 41A3 mouse neuroblastoma ce lls. Neuritogenesis, elicited by adhesion to FN-enriched substrata, wa s reversibly impaired by pretreating these cells with the tyrosine kin ase inhibitor Herbimycin A. This impairment mimicked that operated by Cs+ ions, which selectively inhibited the integrin-mediated activation of K-IR channels. Various phosphotyrosine containing cellular protein s underwent a marked increase upon cell adhesion to FN-coated dishes. This increase was significantly reduced by Cs+ addition. Immunoprecipi tation of pp125(FAK) revealed that the phosphorylation of this kinase and several associated proteins was significantly and reversibly inhib ited by Cs+, indicating that integrin-mediated activation of K-IR chan nels is a limiting step upstream to the phosphorylation of ppl25(FAK) in the commitment to neuritogenesis. (C) 1995 Academic Press, Inc.