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Cyclin-dependent ki...
Cyclin-dependent kinase 5 mediates pleiotrophin-induced endothelial cell migration
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- Lampropoulou, Evgenia (författare)
- Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.
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- Logoviti, Ioanna (författare)
- Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.
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- Koutsioumpa, Marina (författare)
- 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.
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- Hatziapostolou, Maria (författare)
- Nottingham Trent Univ, Sch Sci & Technol, Dept Biosci, Nottingham NG11 8NS, England.
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- Polytarchou, Christos (författare)
- Nottingham Trent Univ, Sch Sci & Technol, Dept Biosci, Nottingham NG11 8NS, England.
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- Skandalis, Spyros S. (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Univ Patras, Dept Chem, Lab Biochem, GR-26504 Patras, Greece
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- Hellman, Ulf (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Fousteris, Manolis (författare)
- Univ Patras, Dept Pharm, Lab Med Chem, GR-26504 Patras, Greece.
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- Nikolaropoulos, Sotirios (författare)
- Univ Patras, Dept Pharm, Lab Med Chem, GR-26504 Patras, Greece.
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- Choleva, Efrosini (författare)
- Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.
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- Lamprou, Margarita (författare)
- Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.
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- Skoura, Angeliki (författare)
- Univ Patras, Comp Engn & Informat Dept, Patras, Greece.
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- Megalooikonomou, Vasileios (författare)
- Univ Patras, Comp Engn & Informat Dept, Patras, Greece.
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- Papadimitriou, Evangelia (författare)
- Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.
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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)
- 2018-04-12
- 2018
- Engelska.
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
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Lampropoulou, Ev ...
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Logoviti, Ioanna
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Koutsioumpa, Mar ...
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Hatziapostolou, ...
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Polytarchou, Chr ...
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Skandalis, Spyro ...
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Hellman, Ulf
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Fousteris, Manol ...
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Nikolaropoulos, ...
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Choleva, Efrosin ...
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Lamprou, Margari ...
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Skoura, Angeliki
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Megalooikonomou, ...
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Papadimitriou, E ...
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Uppsala universitet