tailieunhanh - Báo cáo khoa học: Atypical PKCf is involved in RhoA-dependent mitogenic signaling by the P2Y12 receptor in C6 cells

When nucleotide hydrolysis is prevented, agonists of the P2Y12 receptor enhance the proliferation of C6 glioma cells by RhoA-dependent, protein kinase C (PKC)-dependent activation of the extracellular signal-regulated kinase (ERK) pathway [Claes P, Grobben B, Van Kolen K, Roymans D & Slegers H (2001)Br J Pharmacol134, 402–408; Grobben B, Claes P, Van Kolen K, Roymans D, Fransen P, Sys SU & Slegers H (2001)J Neurochem 78, 1325–1338]. | ềFEBS Journal Atypical PKCf is involved in RhoA-dependent mitogenic signaling by the P2Y12 receptor in C6 cells Kristof Van Kolen and Herman Slegers Laboratory of Cellular Biochemistry Department of BiomedicalSciences University of Antwerp Belgium Keywords extracellular signal-regulated kinase ERK P2Y12 receptor protein kinase Cf PKCf RhoA Rho-associated coiled-coil-containing kinase ROCK Correspondence H. Slegers Department of Biomedical Sciences Cellular Biochemistry University of Antwerp Universiteitsplein 1 B-2610 Wilrijk-Antwerpen Belgium Fax 32 3 8202248 Tel 32 3 8202306 E-mail Present address CNS Research Johnson Johnson PRD Janssen Pharmaceutica Beerse Belgium. Received 3 January 2006 revised 21 February 2006 accepted 27 February 2006 doi When nucleotide hydrolysis is prevented agonists of the P2Y12 receptor enhance the proliferation of C6 glioma cells by RhoA-dependent protein kinase C PKC -dependent activation of the extracellular signal-regulated kinase ERK pathway Claes P Grobben B Van Kolen K Roymans D Slegers H 2001 Br J Pharmacol 134 402-408 Grobben B Claes P Van Kolen K Roymans D Fransen P Sys SU Slegers H 2001 J Neurochem 78 1325-1338 . In this study we show that ERK1 2 phosphorylation was not affected by transfection of the cells with the GPy-subunit-scavenging adrenergic receptor kinase peptide pARK1- 495-689 or with Rap1-GAPII indicating that P2Y12 receptor stimulation enhances 2 phosphorylation by Gia subunit-mediated signaling independently of Rap1 activation. Inhibition of the RhoA downstream effector Rho-associated coiled-coil-containing kinase ROCK with Y-27632 did not affect the P2Y12 receptor-induced increase in ERK1 2 phosphorylation but abrogated the mitogenic response. Involvement of growth factor receptor transactivation in the signaling towards ERK phosphorylation could be ruled out by the lack of an effect of PP2 AG1024 Ag1296 or SU1498 inhibitors of Src insulin-like .

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