Differential regulation of protein tyrosine kinase signalling by Dock and the PTP61F variants

摘要: Tyrosine phosphorylation-dependent signalling is coordinated by the opposing actions of protein tyrosine kinases (PTKs) and phosphatases (PTPs). There a growing list adaptor proteins that interact with PTPs facilitate dephosphorylation substrates. The extent to which any given confers selectivity for substrate in vivo remains unclear. Here we have taken advantage Drosophila melanogaster as model organism explore influence SH3/SH2 Dock on abilities membrane (PTP61Fm)- nuclear (PTP61Fn)-targeted variants PTP61F (the othologue mammalian enzymes PTP1B TCPTP respectively) repress PTK pathways vivo. PTP61Fn effectively repressed eye overgrowth associated activation epidermal growth factor receptor (EGFR), PTK, or expression platelet-derived factor/vascular endothelial (PVR) insulin (InR) PTKs. EGFR PVR-induced mitogen-activated kinase attenuated STAT92E signalling. By contrast, PTP61Fm EGFR- PVR-, but not InR-induced tissue overgrowth. Importantly, coexpression allowed efficient repression overgrowth, did enhance PTP61Fm-mediated inhibition Instead, increased, further exacerbated These results demonstrate selectively enhances attenuation InR underscores specificity importance regulating PTP function