Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/16843
Title: PINI and MEK2 Regulate BPGAPI - Induced ERK Activation and Cell Migration
Authors: PAN QIURONG, CATHERINE
Keywords: BPGAP1; RhoGAP; Mek; Erk; Pin1; WW; PPI; proline-rich
Issue Date: 19-Aug-2009
Source: PAN QIURONG, CATHERINE (2009-08-19). PINI and MEK2 Regulate BPGAPI - Induced ERK Activation and Cell Migration. ScholarBank@NUS Repository.
Abstract: BPGAP1 is a multi-domain Rho GTPase-activating protein (RhoGAP) that promotes Erk activation and cell motility. However, little is known on its regulation. Here we show that the RhoGAP domain interacted with peptidyl-prolyl cis/trans isomerase Pin1 and either wildtype or constitutive-active Mek2 but not with kinase-dead Mek2. Active Mek2 also interacted with Pin1, bridging Pin1 and BPGAP1 in a scaffold manner without protein phosphorylation while promoting the release of the auto-inhibited proline-rich motif, 186-PPLP-189. This, together with 256-DDYGD-260 motif on RhoGAP domain, became accessible to concerted binding by WW and PPI domains of Pin1, respectively. Importantly, Pin1 knockdown augmented BPGAP1 ability to enhance acute Erk activation whereas reintroducing Pin1, but not its catalytic mutant, Pin1-H157A, reversed the effect and inhibited BPGAP1/Mek2-induced cell migration. Active Mek2 could serve as a scaffold that promotes Pin1-BPGAP1 interaction to suppress BPGAP1-induced acute Erk activation and cell motility, thus providing an additional checkpoint for Mek/Erk signalling.
URI: http://scholarbank.nus.edu.sg/handle/10635/16843
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