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 Blood, 1 May 2007, Vol. 109, No. 9, pp. 3679-3686.
Prepublished online as a Blood First Edition Paper on January 9, 2007; DOI 10.1182/blood-2006-11-057315.

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Submitted November 13, 2006
Accepted January 2, 2007

Involvement of Fyn kinase in Kit and integrin-mediated Rac activation, cytoskeletal reorganization and chemotaxis of mast cells

Lionel A Samayawardhena, Reuben Kapur, and Andrew WB Craig*

Dept of Biochemistry, Queen's University, Kingston, Ontario, Canada
Section of Neonatal-Perinatal Medicine, Dept of Pediatrics, Herman B. Wells Center for Pediatrics, Indianapolis, IN, United States

* Corresponding author; email: ac15{at}post.queensu.ca.

Kit receptor and its ligand stem cell factor (SCF) are critical regulators of mast cell production, proliferation, degranulation and chemotaxis. In this study, we investigated how Fyn kinase regulates chemotaxis of mast cells towards SCF. Upon {beta}1 integrin engagement, Fyn-deficient (fyn-/-) mast cells displayed a striking defect in cell spreading, lamellapodia formation compared to wild-type mast cells. The hematopoietic-specific Src family kinases (Lyn/Fgr/Hck) were not required for initial SCF-induced cell spreading. Reduced SCF-induced activation of Rac1 and Rac2 GTPases, p38 Mitogen-activated protein kinase, and filamentous actin polymerization was observed in fyn-/- mast cells compared to wild-type mast cells. Retroviral-mediated expression of Fyn, constitutively active Rac2 or phosphatidylinositol-3 kinase (PI3K) in fyn-/- mast cells, rescued defects in SCF-induced cell polarization and chemotaxis of Fyn-deficient mast cells. Thus, we conclude that Fyn kinase plays a unique role upstream of PI3K and Rac GTPases to promote the reorganization of the cytoskeleton during mast cell spreading and chemotaxis.


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B. Huang, Z. Lei, G.-M. Zhang, D. Li, C. Song, B. Li, Y. Liu, Y. Yuan, J. Unkeless, H. Xiong, et al.
SCF-mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment
Blood, August 15, 2008; 112(4): 1269 - 1279.
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