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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. This Article Full Text (PDF) All Versions of this Article: blood-2006-11-057315v1 109/9/3679    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Samayawardhena, L. A Articles by Craig, A. W. Search for Related Content PubMed PubMed Citation Articles by Samayawardhena, L. A Articles by Craig, A. W. Social Bookmarking                   What's this?  Previous Article  |  Next Article  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 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Mithraprabhu and K. L Loveland Control of KIT signalling in male germ cells: what can we learn from other systems? Reproduction, November 1, 2009; 138(5): 743 - 757. [Abstract] [Full Text] [PDF] V. A. McPherson, N. Sharma, S. Everingham, J. Smith, H. H. Zhu, G.-S. Feng, and A. W. B. Craig SH2 Domain-Containing Phosphatase-2 Protein-Tyrosine Phosphatase Promotes Fc{epsilon}RI-Induced Activation of Fyn and Erk Pathways Leading to TNF{alpha} Release from Bone Marrow-Derived Mast Cells J. Immunol., October 15, 2009; 183(8): 4940 - 4947. [Abstract] [Full Text] [PDF] M. Mani, S. Venkatasubrahmanyam, M. Sanyal, S. Levy, A. Butte, K. Weinberg, and T. Jahn Wiskott-Aldrich syndrome protein is an effector of Kit signaling Blood, October 1, 2009; 114(14): 2900 - 2908. [Abstract] [Full Text] [PDF] J. Aramburu and C. Lopez-Rodriguez Brx Shines a Light on the Route from Hyperosmolarity to NFAT5 Sci. Signal., April 7, 2009; 2(65): pe20 - pe20. [Abstract] [Full Text] [PDF] T. Zhao, D. Wang, S. Y. Cheranov, M. Karpurapu, K. R. Chava, V. Kundumani-Sridharan, D. A. Johnson, J. S. Penn, and G. N. Rao A novel role for activating transcription factor-2 in 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis J. Lipid Res., March 1, 2009; 50(3): 521 - 533. [Abstract] [Full Text] [PDF] L. A. Samayawardhena and C. J. Pallen Protein-tyrosine Phosphatase {alpha} Regulates Stem Cell Factor-dependent c-Kit Activation and Migration of Mast Cells J. Biol. Chem., October 24, 2008; 283(43): 29175 - 29185. [Abstract] [Full Text] [PDF] 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. [Abstract] [Full Text] [PDF]

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