Cyclin-dependent kinase 5 mediates pleiotrophin-induced endothelial cell migration

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Fältnamn	Indikatorer	Metadata
000		04945naa a2200481 4500
001		oai:DiVA.org:uu-352477
003		SwePub
008		181106s2018 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3524772 URI
024	7	a https://doi.org/10.1038/s41598-018-24326-x2 DOI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Lampropoulou, Evgeniau Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.4 aut
245	1 0	a Cyclin-dependent kinase 5 mediates pleiotrophin-induced endothelial cell migration
264		c 2018-04-12
264	1	b NATURE PUBLISHING GROUP,c 2018
338		a electronic2 rdacarrier
520		a Pleiotrophin (PTN) stimulates endothelial cell migration through binding to receptor protein tyrosine phosphatase beta/zeta (RPTP beta/zeta) and alpha(nu)beta(3) integrin. Screening for proteins that interact with RPTP beta/zeta and potentially regulate PTN signaling, through mass spectrometry analysis, identified cyclindependent kinase 5 (CDK5) activator p35 among the proteins displaying high sequence coverage. Interaction of p35 with the serine/threonine kinase CDK5 leads to CDK5 activation, known to be implicated in cell migration. Protein immunoprecipitation and proximity ligation assays verified p35-RPTP beta/zeta interaction and revealed the molecular association of CDK5 and RPTP beta/zeta. In endothelial cells, PTN activates CDK5 in an RPTP beta/zeta- and phosphoinositide 3-kinase (PI3K)-dependent manner. On the other hand, c-Src, alpha(nu)beta(3) and ERK1/2 do not mediate the PTN-induced CDK5 activation. Pharmacological and genetic inhibition of CDK5 abolished PTN-induced endothelial cell migration, suggesting that CDK5 mediates PTN stimulatory effect. A new pyrrolo[2,3-alpha] carbazole derivative previously identified as a CDK1 inhibitor, was found to suppress CDK5 activity and eliminate PTN stimulatory effect on cell migration, warranting its further evaluation as a new CDK5 inhibitor. Collectively, our data reveal that CDK5 is activated by PTN, in an RPTP beta/zeta-dependent manner, regulates PTN-induced cell migration and is an attractive target for the inhibition of PTN pro-angiogenic properties.
650	7	a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe
650	7	a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng
700	1	a Logoviti, Ioannau Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.4 aut
700	1	a Koutsioumpa, Marinau Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.;Univ Calif Los Angeles, David Geffen Sch Med, Vatche & Tamar Manoukian Div Digest Dis, Ctr Syst Biomed, Los Angeles, CA 90095 USA.4 aut
700	1	a Hatziapostolou, Mariau Nottingham Trent Univ, Sch Sci & Technol, Dept Biosci, Nottingham NG11 8NS, England.4 aut
700	1	a Polytarchou, Christosu Nottingham Trent Univ, Sch Sci & Technol, Dept Biosci, Nottingham NG11 8NS, England.4 aut
700	1	a Skandalis, Spyros S.u Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Univ Patras, Dept Chem, Lab Biochem, GR-26504 Patras, Greece4 aut
700	1	a Hellman, Ulfu Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi4 aut0 (Swepub:uu)ulfhm
700	1	a Fousteris, Manolisu Univ Patras, Dept Pharm, Lab Med Chem, GR-26504 Patras, Greece.4 aut
700	1	a Nikolaropoulos, Sotiriosu Univ Patras, Dept Pharm, Lab Med Chem, GR-26504 Patras, Greece.4 aut
700	1	a Choleva, Efrosiniu Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.4 aut
700	1	a Lamprou, Margaritau Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.4 aut
700	1	a Skoura, Angelikiu Univ Patras, Comp Engn & Informat Dept, Patras, Greece.4 aut
700	1	a Megalooikonomou, Vasileiosu Univ Patras, Comp Engn & Informat Dept, Patras, Greece.4 aut
700	1	a Papadimitriou, Evangeliau Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.4 aut
710	2	a Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.b Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.;Univ Calif Los Angeles, David Geffen Sch Med, Vatche & Tamar Manoukian Div Digest Dis, Ctr Syst Biomed, Los Angeles, CA 90095 USA.4 org
773	0	t Scientific Reportsd : NATURE PUBLISHING GROUPg 8q 8x 2045-2322
856	4	u https://doi.org/10.1038/s41598-018-24326-xy Fulltext
856	4	u https://uu.diva-portal.org/smash/get/diva2:1261205/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4	u https://www.nature.com/articles/s41598-018-24326-x.pdf
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-352477
856	4 8	u https://doi.org/10.1038/s41598-018-24326-x

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By the author/editor: Lampropoulou, Ev ...; Logoviti, Ioanna; Koutsioumpa, Mar ...; Hatziapostolou, ...; Polytarchou, Chr ...; Skandalis, Spyro ...; show more...; Hellman, Ulf; Fousteris, Manol ...; Nikolaropoulos, ...; Choleva, Efrosin ...; Lamprou, Margari ...; Skoura, Angeliki; Megalooikonomou, ...; Papadimitriou, E ...; show less...

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