Lyn is required for normal stem cell factor-induced proliferation and chemotaxis of primary hematopoietic cells

Stem cell factor (SCF) binds to c-Kit and is an important mediator of survi val, growth, and function of hematopoietic progenitor cells and mast cells. Lyn and other Src family members are activated by SCF and associate with p hosphorylated tyrosine residues in the c-Kit juxtamembrane region. However, studies using c-Kit mutants incapable of directly recruiting Src family me mbers suggest this kinase family plays a minimal role in c-Kit stimulus-res ponse coupling mechanisms, The objective of this study was to specifically target Lyn and subsequently address its role in SCF-mediated responses of p rimary hematopoietic progenitor cells and mast cells, To this end, a domina nt-inhibitory Lyn mutant and Lyn-deficient mice were used. Transfection of normal murine mast cells with kinase-inactive Lyn impaired SCF-induced grow th. Further, SCF-induced proliferation and chemotaxis of Lyn-deficient mast cells were less than for wild-type mast cells. SCF-induced growth of proge nitor cells lacking Lyn was also reduced compared with that bf wild-type pr ogenitor cells. Impairment of SCF-mediated responses of Lyn-deficient mast cells and progenitor cells did not result from reductions in surface expres sion of c-Kit, These studies demonstrate that Lyn is required for normal SC F-mediated responses of primary progenitors and for a differentiated lineag e. (C) 2001 by The American Society of Hematology.