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

The relationships between the integrin-mediated activation of inward rectifyier K+ channels (K-IR), the phosphorylation of pp125(FAK) and the rescue of neuritogenesis were studied in 41A3 mouse neuroblastoma cells. Neuritogenesis, elicited by adhesion to FN-enriched substrata, was reversibly impaired by pretreating these cells with the tyrosine kinase 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 proteins underwent a marked increase upon cell adhesion to FN-coated dishes. This increase was significantly reduced by Cs+ addition. Immunoprecipitation of pp125(FAK) revealed that the phosphorylation of this kinase and several associated proteins was significantly and reversibly inhibited by Cs+, indicating that integrin-mediated activation of K-IR channels is a limiting step upstream to the phosphorylation of ppl25(FAK) in the commitment to neuritogenesis. (C) 1995 Academic Press, Inc.