Tyrosine kinase-deficient Wvc-kit induces mast cell adhesion and chemotaxis

W/Wvmice are deficient in tissue mast cells, and mast cells cultured from these mice do not proliferate in response to the c-kit ligand, stem cell factor (SCF). In this paper, we report that mouse bone marrow cultured mast cells derived from W/Wvmice do adhere to fibronectin in the presence of SCF and exhibit chemotaxis to SCF, and we explore this model for the understanding of c-kit-mediated signaling pathways. Both in vitro and in vivo (in intact cells) phosphorylation experiments demonstrated a low residual level of W/Wvc-kit protein phosphorylation. SCF-induced responses in W/Wvmast cells were abolished by the tyrosine kinase inhibitor herbimycin A and by the phospatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin but were not affected by protein kinase C inhibitors. These observations are consistent with the conclusions that Wvc-kit initiates a signaling process that is PI 3-kinase dependent and that mutated Wvc-kit retains the ability to initiate mast cell adhesion and migration.

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