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

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Abstract
Stem cell factor (SCF) binds to c-Kit and is an important mediator of survival, growth, and function of hematopoietic progenitor cells and mast cells. Lyn and other Src family members are activated by SCF and associate with phosphory- lated tyrosine residues in the c-Kit jux- tamembrane region. However, studies us- ing c-Kit mutants incapable of directly recruiting Src family members suggest this kinase family plays a minimal role in c-Kit stimulus-response coupling mecha- nisms. The objective of this study was to specifically target Lyn and subsequently address its role in SCF-mediated re- sponses of primary hematopoietic pro- genitor cells and mast cells. To this end, a dominant-inhibitory Lyn mutant and Lyn- deficient mice were used. Transfection of normal murine mast cells with kinase- inactive Lyn impaired SCF-induced growth. Further, SCF-induced prolifera- tion and chemotaxis of Lyn-deficient mast cells were less than for wild-type mast cells. SCF-induced growth of progenitor cells lacking Lyn was also reduced com- pared with that of wild-type progenitor cells. Impairment of SCF-mediated re- sponses of Lyn-deficient mast cells and progenitor cells did not result from reduc- tions in surface expression of c-Kit. These studies demonstrate that Lyn is required for normal SCF-mediated responses of primary progenitors and for a differenti- ated lineage. (Blood. 2001;98:343-350)

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