Figure 2.

Binding of specific signalling proteins to phosphorylated tyrosine residues on KIT following receptor activation and the subsequent signalling events leading to mast cell responses. For clarity, only one receptor is shown in the figure. SCF-induced KIT dimerization enhances the tyrosine kinase activity associated with the split catalytic domain. This results in phosphorylation of specific tyrosine residues within the cytosolic domain of KIT. The tyrosine kinase, Lyn, may also contribute to this response. The consequential recruitment of critical signalling molecules such as the tyrosine kinases, Lyn and Fyn, the adaptor molecules, SHC and Grb2 and the signalling enzymes, PI3K and phospholipase Cγ, results in the activation of the Ras–Raf–mitogen-activated protein kinase (MAPK) pathway, the enhancement of intracellular calcium levels, and the activation of transcription factors leading to mast cell growth, differentiation and survival; enhanced cell migration and chemotaxis; and cytokine production. Activation of the JAK2 and STAT1/3/5 likely contributes to these responses. Concurrent with these events, KIT induces activation of the Tec kinase Btk and the adaptor molecule NTAL (non-T-cell activation linker), resulting in an enhancement of antigen-mediated degranulation and cytokine production. (For further details, please refer to Broudy, 1997; Linnekin, 1999; Tkaczyk et al., 2004; Iwaki et al., 2005; Lennartsson et al., 2005; Roskoski, 2005a, 2005b; Gilfillan and Tkaczyk, 2006; Reber et al., 2006.)