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  • Lampropoulou, EvgeniaUniv Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece. (author)

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

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-04-12
  • NATURE PUBLISHING GROUP,2018
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-352477
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-352477URI
  • https://doi.org/10.1038/s41598-018-24326-xDOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Logoviti, IoannaUniv Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece. (author)
  • Koutsioumpa, MarinaUniv 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. (author)
  • Hatziapostolou, MariaNottingham Trent Univ, Sch Sci & Technol, Dept Biosci, Nottingham NG11 8NS, England. (author)
  • Polytarchou, ChristosNottingham Trent Univ, Sch Sci & Technol, Dept Biosci, Nottingham NG11 8NS, England. (author)
  • Skandalis, Spyros S.Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Univ Patras, Dept Chem, Lab Biochem, GR-26504 Patras, Greece (author)
  • Hellman, UlfUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)ulfhm (author)
  • Fousteris, ManolisUniv Patras, Dept Pharm, Lab Med Chem, GR-26504 Patras, Greece. (author)
  • Nikolaropoulos, SotiriosUniv Patras, Dept Pharm, Lab Med Chem, GR-26504 Patras, Greece. (author)
  • Choleva, EfrosiniUniv Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece. (author)
  • Lamprou, MargaritaUniv Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece. (author)
  • Skoura, AngelikiUniv Patras, Comp Engn & Informat Dept, Patras, Greece. (author)
  • Megalooikonomou, VasileiosUniv Patras, Comp Engn & Informat Dept, Patras, Greece. (author)
  • Papadimitriou, EvangeliaUniv Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece. (author)
  • Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.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. (creator_code:org_t)

Related titles

  • In:Scientific Reports: NATURE PUBLISHING GROUP82045-2322

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