title: A crucial role for Lyn in TIMP-1 erythroid cell survival signalling pathway.
abstract: TIMP-1, a well-known MMP inhibitor, displays other biological activities such as cell survival, proliferation and differentiation in hematopoietic cells. In this report, we investigated the role of the Src-related kinase Lyn in TIMP-1 induced UT-7 erythroleukemic cell survival. We showed that (i) tyrosine 507 of Lyn was dephosphorylated and Lyn kinase activity enhanced by TIMP-1, (ii) Lyn silencing suppressed TIMP-1 anti-apoptotic activity and (iii) Lyn was activated upstream the JAK2/PI 3-kinase/Akt pathway. Our data suggest a novel role for Lyn in erythroid cell survival.
authors.affiliation: Université de Reims Champagne Ardenne, CNRS FRE 3481 MEDyC, Laboratoire SiRMa, SFR CAP Santé, Moulin de la Housse, BP 1039, 51687 Reims, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Bridoux
authors.forename: Nicolas
authors.initials: N
authors.lastname: Etique
authors.forename: Elise
authors.initials: E
authors.lastname: Lambert
authors.forename: Jessica
authors.initials: J
authors.lastname: Thevenard
authors.forename: Marie-Line
authors.initials: ML
authors.lastname: Sowa
authors.forename: Nicolas
authors.initials: N
authors.lastname: Belloy
authors.forename: Manuel
authors.initials: M
authors.lastname: Dauchez
authors.forename: Laurent
authors.initials: L
authors.lastname: Martiny
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charpentier
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019869:Phosphatidylinositol 3-Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D051058:Oncogene Protein v-akt