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Fig. 8. Model of Abl-dependent proliferation in fibroblasts. Endogenous Abl kinases directly phosphorylate SHP-2 on Y580, which increases sustained ERK activation in response to PDGF (Figs 3 and 6) (Araki et al., 2003). Abl kinases also induce phosphorylation of Y63 and Y279 (Fig. 2B) presumably by activating unknown tyrosine kinases (X and Y). Phosphorylation of Y63 potentiates mitogenic signaling in fibroblasts (Fig. 6C,D), and phosphorylation of Y279 negatively regulates ERK activation (Fig. 6A,B) and proliferation (Fig. 6C,D). Abl kinases also activate a Rac-JNK pathway (Boureux et al., 2005), which may be dependent or independent of SHP-2 (Yu et al., 2006) (dotted lines).

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