title: Inhibition of H-Ras and MAPK is compensated by PKC-dependent pathways in annexin A6 expressing cells.
abstract: High-density lipoprotein (HDL)-induced activation of the Ras/MAPK pathway can be mediated by protein kinase C (PKC)-dependent and independent pathways. Although both pathways co-exist in cells, we showed that binding of HDL to scavenger receptor BI (SR-BI) in CHO cells activates Ras and MAPK in a PKC-independent manner. We have recently identified that HDL-induced activation of Ras and Raf-1 is reduced in annexin A6 expressing CHO cells (CHOanx6). In the present study we demonstrate that despite the loss of Ras and Raf-1 activity, HDL induces MAPK phosphorylation in CHOanx6 cells. Since annexin A6 is a PKCalpha-binding protein we therefore investigated the possible involvement of PKC in HDL-induced Ras and MAPK activation in CHOanx6 cells. Taken together our findings demonstrate that HDL-induced H-Ras and MAPK activation is PKC-dependent in cells expressing annexin A6 to compensate for the loss of PKC-independent activation of H-Ras and MAPK.
authors.affiliation: Departament de Biologia Cellular, Facultat de Medicina, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, and Centre for Immunology, St. Vincent's Hospital, Sydney, NSW, Australia.
authors.forename: Carles
authors.initials: C
authors.lastname: Rentero
authors.forename: Rachael
authors.initials: R
authors.lastname: Evans
authors.forename: Peta
authors.initials: P
authors.lastname: Wood
authors.forename: Francesc
authors.initials: F
authors.lastname: Tebar
authors.forename: Sandra
authors.initials: S
authors.lastname: Vilà de Muga
authors.forename: Laia
authors.initials: L
authors.lastname: Cubells
authors.forename: Iñaki
authors.initials: I
authors.lastname: de Diego
authors.forename: Toni E
authors.initials: TE
authors.lastname: Hayes
authors.forename: William E
authors.initials: WE
authors.lastname: Hughes
authors.forename: Albert
authors.initials: A
authors.lastname: Pol
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
authors.forename: Carlos
authors.initials: C
authors.lastname: Enrich
authors.forename: Thomas
authors.initials: T
authors.lastname: Grewal
mesh_terms: D000818:Animals; D017317:Annexin A6 / Q000096:biosynthesis*; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D008075:Lipoproteins, HDL / Q000502:physiology; D053440:Lipoproteins, HDL3; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D015398:Signal Transduction; D018631:ras Proteins / Q000037:antagonists & inhibitors*
chemical_list: D017317:Annexin A6; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D002784:Cholesterol; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D018631:ras Proteins; D002118:Calcium