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Blood, 15 July 2001, Vol. 98, No. 2, pp. 343-350
HEMATOPOIESIS
Lyn is required for normal stem cell factor-induced
proliferation and chemotaxis of primary hematopoietic cells
Bridget O'Laughlin-Bunner,
Nina Radosevic,
Marcia L. Taylor,
Shivakrupa,
Candy DeBerry,
Dean D. Metcalfe,
Meijuan Zhou,
Clifford Lowell, and
Diana Linnekin
From the Basic Research Laboratory, Division of Basic
Sciences, National Cancer Institute-Frederick; the Laboratory of
Allergic Diseases, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, MD; and the
Department of Laboratory Medicine, School of Medicine, University of
California, San Francisco.
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 phosphorylated tyrosine residues in the c-Kit
juxtamembrane region. However, studies using c-Kit mutants incapable of
directly recruiting Src family members suggest this kinase family plays
a minimal role in c-Kit stimulus-response coupling mechanisms. The
objective of this study was to specifically target Lyn and subsequently
address its role in SCF-mediated responses of primary hematopoietic
progenitor 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 proliferation 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 compared with that of
wild-type progenitor cells. Impairment of SCF-mediated responses of
Lyn-deficient mast cells and progenitor cells did not result from
reductions in surface expression of c-Kit. These studies demonstrate
that Lyn is required for normal SCF-mediated responses of primary
progenitors and for a differentiated lineage.
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