Steel factor and c-kit regulate cell-matrix adhesion.
Steel (SI) and white spotting (W) loci encode steel factor (c-kit ligand) and the c-kit tyrosine kinase receptor, respectively. Mutations at these loci affect migration and differentiation of primordial germ cells, neural crest-derived melanoblasts, and hematopoietic cells. In these processes, cell adhesion molecules are hypothesized to be crucial. We have examined the role of steel factor and c-kit in cell-extracellular matrix adhesion using bone marrow-derived mast cells as a model system. Steel factor stimulates mast cells to bind to fibronectin and, to a lesser extent, to vitronectin, whereas interleukin-3 and interleukin-4, which are also mast cell growth factors, do not. Activation of adhesiveness is transient, occurs at concentrations of steel factor 100-fold lower than required for growth stimulation, and requires the integrin VLA-5. Mast cells from c-kit mutant mice adhere to fibronectin on stimulation with phorbol 12-myristate 13-acetate (PMA), but not on stimulation with steel factor, indicating that stimulation of integrin adhesiveness requires activation of the c-kit protein tyrosine kinase. By contrast, c-kit mutant and wild-type mast cells adhere equally well to COS cells expressing membrane-anchored steel factor, showing that the kinase activity of c-kit is not required for adhesion directly mediated by c-kit. Our findings suggest that regulation of adhesion is an important biologic function of steel factor.
Kinashi
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Center For Blood Research, Boston, MA 02115.
Springer
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D000818:Animals; D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism; D016298:Hematopoietic Cell Growth Factors / Q000235:genetics / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007700:Kinetics; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D019089:Stem Cell Factor; D014162:Transfection; D019096:Vitronectin
D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D006023:Glycoproteins; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D019096:Vitronectin; D015847:Interleukin-4; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases