SWAP-70 Regulates c-kit-Induced Mast Cell Activation, Cell-Cell Adhesion, and Migration†

AUTOR(ES)

Sivalenka, Raja Rajeswari

FONTE

American Society for Microbiology

RESUMO

SWAP-70, an unusual phosphatidylinositol-3-kinase-dependent protein that interacts with the RhoGTPase Rac, is highly expressed in mast cells. Cultured bone marrow mast cells (BMMC) from SWAP-70−/− mice are reduced in FcɛRI-triggered degranulation. This report describes the hitherto-unknown role of SWAP-70 in c-kit receptor signaling, a key proliferation and differentiation pathway in mast cells. Consistent with the role of Rac in cell motility and regulation of the actin cytoskeleton, mutant cells show abnormal actin rearrangements and are deficient in migration in vitro and in vivo. SWAP-70−/− BMMC are impaired in calcium flux, in proper translocation and activity of Akt kinase (required for mast cell activation and survival), and in translocation of Rac1 and Rac2 upon c-kit stimulation. Adhesion to fibronectin is reduced, but homotypic cell association induced through c-kit is strongly increased in SWAP-70−/− BMMC. Homotypic association requires extracellular Ca2+ and depends on the integrin αLβ2 (LFA-1). ERK is hyperactivated upon c-kit signaling in adherent and dispersed mutant cells. Together, we suggest that SWAP-70 is an important regulator of specific effector pathways in c-kit signaling, including mast cell activation, migration, and cell adhesion.

Documentos Relacionados

• A Saccharomyces gene family involved in invasive growth, cell–cell adhesion, and mating
• Association of SWAP-70 with the B cell antigen receptor complex
• Sok2 Regulates Yeast Pseudohyphal Differentiation via a Transcription Factor Cascade That Regulates Cell-Cell Adhesion
• Cell-cell interactions in synovitis: Endothelial cells and immune cell migration
• Microtubule Disruption in Keratinocytes Induces Cell-Cell Adhesion through Activation of Endogenous E-Cadherin