Characterization of HSP27 phosphorylation induced by microtubule interfering agents: implication of p38 signalling pathway.
Vincristine and paclitaxel are widely used antitumoral drugs that interfere with microtubule dynamics. We have previously demonstrated that vincristine induces phosphorylation of HSP27 at serine 82 in MCF-7 cells. In this report, we show that vincristine also causes phosphorylation of serines 78 and 15. Moreover, we demonstrate that phosphorylation of this chaperone is induced by the p38 signalling pathway while the JNK pathway is not implicated. Differences between vincristine and paclitaxel treatments are also appreciated. Thus, while vincristine induces a strong phosphorylation of the three serines, paclitaxel induces a weak phosphorylation of serine 78 and has no effect over serines 82 and 15 phosphorylation. Interestingly, pre-treatment of cells with a ten-fold excess of paclitaxel abolishes vincristine-induced phosphorylation of HSP27.
Casado
Pedro
P
Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33071 Oviedo, Spain.
Zuazua-Villar
Pedro
P
Prado
Miguel A
MA
Valle
Eva Del
ED
Iglesias
Juan Manuel
JM
Martínez-Campa
Carlos
C
Lazo
Pedro S
PS
Ramos
Sofía
S
D045744:Cell Line, Tumor; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology*; D008870:Microtubules / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D012694:Serine / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*; D014750:Vincristine / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D050257:Tubulin Modulators; D012694:Serine; D014750:Vincristine; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D017239:Paclitaxel