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Both adhesion to immobilized vitronectin and FcɛRI cross‐linking cause enhanced focal adhesion kinase phosphorylation in murine mast cells
Author(s) -
Bhattacharyya S. P.,
Mekori Y. A.,
Hoh D.,
Paolini R.,
Metcalfe D. D.,
Bianchine P. J.
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00883.x
Subject(s) - tyrosine phosphorylation , focal adhesion , microbiology and biotechnology , phosphorylation , ptk2 , signal transduction , tyrosine kinase , tyrosine , integrin , mast cell , vitronectin , receptor tyrosine kinase , chemistry , cell adhesion , biology , protein kinase c , fibronectin , biochemistry , receptor , mitogen activated protein kinase kinase , immunology , cell , extracellular matrix
Summary Murine mast cells adhere spontaneously to plate‐bound vitronectin (VN PB ) via α v ‐containing integrins, and this adhesive interaction results in an augmented interleukin‐3 (IL‐3)‐dependent mast‐cell proliferation. In this report we demonstrate that the activation of murine mast cells through α v ‐integrin, as well as through the high affinity immunoglobulin E (IgE) receptor (FcɛRI), results in enhanced tyrosine phosphorylation of focal adhesion kinase (FAK), a cytoplasmic protein tyrosine kinase involved in mitogenic and oncogenic signal transduction. While mast cell adhesion to VN PB resulted in enhanced FAK phosphorylation, treatment with soluble vitronectin (VN SOL ) failed to do so. Spontaneous mast cell adhesion to entactin (EN) did not induce tyrosine phosphorylation of FAK, demonstrating that not all adhesive interactions lead to the same sequence of biochemical events. Because FAK has intrinsic tyrosine kinase activity, we examined whether activating mast cells via α v ‐integrins, or via FcɛRI‐cross‐linking stimulated the in vitro kinase activity of FAK. Both pathways were found independently to activate FAK in mast cells and together appeared additive. Protein kinase C depletion in mast cells and calcium depletion in the medium caused decreased tyrosine phosphorylation of FAK, indicating that optimal tyrosine phosphorylation of FAK is regulated by both pathways. These data are consistent with the conclusion that the tyrosine phosphorylation of FAK represents at least one example of a point of convergence in the intracellular tyrosine phosphorylation cascades induced by α v integrin‐and FcɛRI‐mediated signal transduction pathways in mast cells.