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Stem Cell Factor-Induced Migration of Mast Cells Requires p38 Mitogen-Activated Protein Kinase Activity

https://doi.org/10.1006/excr.2001.5239Get rights and content

Abstract

Stem cell factor (SCF) can be considered a cardinal cytokine in mast cell biology as it affects mast cell differentiation, survival, and migration. The objective of this study was to investigate the role of two mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase (ERK) and p38, in SCF-induced cell migration. This was examined in mouse mast cells by using PD 098059 and SB203580, which are specific inhibitors of mitogen-induced extracellular kinase (MEK) and p38 MAP kinase, respectively. SCF induced a rapid and transient activation of ERK and p38 in a dose-dependent manner. Inhibition of p38 activity by SB203580 was paralleled with a marked reduction of migration toward SCF, whereas the effect of the MEK inhibitor was less pronounced. This is the first report of a physiological function of SCF-dependent activation of p38. Whether p38-mediated mast cell migration is a possible target for suppression of mast cell hyperplasia remains to be determined.

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      When stem cell factor (SCF; also known as Kit ligand) binds to it receptor Kit on mast cell membrane, it stimulates various cellular responses such as degranulation, secretion of various mediators, proliferation, survival and differentiation (Moon et al., 1998; Okayama and Kawakami, 2006; Orinska et al., 2010; Simon et al., 2008). Stimulation of mast cells with SCF triggers a cascade of events leading to activation of Fyn, Syk, protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs), accompanied by increase of intracellular Ca2+ concentration (Blume-Jensen et al., 1994; Okuda et al., 1992; Sundstrom et al., 2001). Mast cells are a major source of PGD2 and LTC4, a parent cysteinyl leukotriene (Diaz et al., 2006; Murakami et al., 1994, 1995).

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    This work was supported by grants from the Swedish Cancer Society, Ollie and Elof Ericssons Foundation, King Gustaf V's 80 Years Foundation, Selanders Foundation, Göran Gustavssons Foundation, and Hans von Kantzow's Foundation.

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    To whom reprint requests should be addressed. Fax: +46 18 558931. E-mail: [email protected].

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