PTP-PEST controls EphA3 activation and ephrin-induced cytoskeletal remodelling.

摘要: Eph receptors and their corresponding membrane-bound ephrin ligands regulate cell positioning establish tissue patterns during embryonic oncogenic development. Emerging evidence suggests that assembly of polymeric signalling clusters relies on cytoskeletal reorganisation underlies regulation by protein tyrosine phosphatases (PTPs). PTP-PEST (also known as PTPN12) is a central regulator actin dynamics. Here, we demonstrate an N-terminal fragment PTP-PEST, generated through ephrinA5-triggered spatially confined cleavage mediated caspase-3, attenuates EphA3 receptor activation its internalisation. Isolation within intact plasma membrane fragments obtained detergent-free fractionation reveals stimulation cells with triggers effective recruitment this catalytically active truncated form together key focal adhesion proteins. Importantly, modulation polymerisation using pharmacological dominant-negative approaches affects phosphorylation in similar manner to overexpression PTP-PEST. We conclude regulates both affecting remodelling direct action PTP controlling phosphorylation, indicating multifaceted signalling.