title: MAP kinase p38 is a novel target of CacyBP/SIP phosphatase.
abstract: Mitogen-activated protein (MAP) kinases are important players in cellular signaling pathways. Recently, it has been shown that CacyBP/SIP serves as a phosphatase for one of the MAP kinases, ERK1/2. Through dephosphorylation of this kinase CacyBP/SIP modulates the transcriptional activity of Elk-1 and the activity of the CREB-BDNF pathway. In this work, using NB2a cell lysate and recombinant proteins, we show that CacyBP/SIP binds and dephosphorylates another member of the MAP kinase family, p38. Analysis of recombinant full-length CacyBP/SIP and its three major domains, N-terminal, middle CS and C-terminal SGS, indicates that the middle CS domain is responsible for p38 dephosphorylation. Moreover, we show that CacyBP/SIP might be implicated in response to oxidative stress. Dephosphorylation of phospho-p38 by CacyBP/SIP in NB2a cells treated with hydrogen peroxide is much more effective than in control ones. In conclusion, involvement of CacyBP/SIP in the regulation of p38 kinase activity, in addition to that of ERK1/2, might point to the function of CacyBP/SIP in pro-survival and pro-apoptotic pathways.
authors.affiliation: Laboratory of Calcium Binding Proteins, Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland.
authors.forename: Agnieszka M
authors.initials: AM
authors.lastname: Topolska-Woś
authors.affiliation: Laboratory of Calcium Binding Proteins, Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland.
authors.forename: Sara
authors.initials: S
authors.lastname: Rosińska
authors.affiliation: Laboratory of Calcium Binding Proteins, Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland. a.filipek@nencki.gov.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Filipek
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation / Q000502:physiology; D000072417:Protein Domains; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C111922:Cacybp protein, mouse; D002135:Calcium-Binding Proteins; C494113:Elk1 protein, mouse; D050807:ets-Domain Protein Elk-1; D048051:p38 Mitogen-Activated Protein Kinases
keywords: CacyBP/SIP; ERK1/2; MAPK; NB2a; Oxidative stress; p38 kinase