PMID:15542837

Citation	Sivalenka, RR and Jessberger, R (2004) SWAP-70 regulates c-kit-induced mast cell activation, cell-cell adhesion, and migration. Mol. Cell. Biol. 24:10277-88
Abstract	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 FcepsilonRI-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 Ca(2+) and depends on the integrin alpha(L)beta(2) (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.
Links	PubMed PMC529030 Online version:10.1128/MCB.24.23.10277-10288.2004
Keywords	Actins/metabolism; Animals; Calcium/metabolism; Cell Adhesion; Cell Differentiation; Cell Membrane/metabolism; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cytoplasm/metabolism; Cytoskeleton/metabolism; DNA-Binding Proteins/metabolism; DNA-Binding Proteins/physiology; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Inhibitors/pharmacology; Extracellular Signal-Regulated MAP Kinases/metabolism; Fibronectins/metabolism; Flavonoids/pharmacology; Glutathione Transferase/metabolism; Guanine Nucleotide Exchange Factors/metabolism; Guanine Nucleotide Exchange Factors/physiology; Lymphocyte Function-Associated Antigen-1/metabolism; Mast Cells/cytology; Mice; Mice, Knockout; Mutation; Nuclear Proteins/metabolism; Nuclear Proteins/physiology; Protein Transport; Protein-Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-kit/metabolism; Signal Transduction; Stem Cell Factor/metabolism; Subcellular Fractions/metabolism; Time Factors; rac GTP-Binding Proteins/metabolism; rac1 GTP-Binding Protein/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:SWP70	involved_in	GO:0033633: negative regulation of cell-cell adhesion mediated by integrin	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:SWP70		GO:0060754: positive regulation of mast cell chemotaxis	ECO:0000315:		P		Figure 1, SWAP-70 KOs display reduced migration of bone marrow mast cells.	complete CACAO 8817
MOUSE:SWP70		GO:0008064: regulation of actin polymerization or depolymerization	ECO:0000315:		P		Figure 2, SWAP-70 KOs exhibit altered regulation of f-actin filaments.	complete CACAO 8818
MOUSE:SWP70		GO:0032880: regulation of protein localization	ECO:0000315:		P		Figure 3, SWAP-70 KOs display decreased localization of Rac1 and Rac2 to the cell periphery.	complete CACAO 8819
MOUSE:SWP70		GO:0007204: elevation of cytosolic calcium ion concentration	ECO:0000315:		P		Figure 4, SWAP-70 KOs don't see the same rapid elevation in Ca2+ ions within the cell that a WT cell does after stimulation.	complete CACAO 8820
MOUSE:SWP70		GO:0033633: negative regulation of cell-cell adhesion mediated by integrin	ECO:0000315:		P		Figure 7, SWAP-70 KOs adhere much more than the WT cells; this adhesion was found to be dependent on the integrin LFA-1.	complete CACAO 8821
MOUSE:SWP70	involved_in	GO:0060754: positive regulation of mast cell chemotaxis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:SWP70	involved_in	GO:0008064: regulation of actin polymerization or depolymerization	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:SWP70	involved_in	GO:0032880: regulation of protein localization	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:SWP70	involved_in	GO:0007204: positive regulation of cytosolic calcium ion concentration	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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