Inhibition of H-Ras and MAPK is compensated by PKC-dependent pathways in annexin A6 expressing cells.
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.
Rentero
Carles
C
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.
Evans
Rachael
R
Wood
Peta
P
Tebar
Francesc
F
Vilà de Muga
Sandra
S
Cubells
Laia
L
de Diego
Iñaki
I
Hayes
Toni E
TE
Hughes
William E
WE
Pol
Albert
A
Rye
Kerry-Anne
KA
Enrich
Carlos
C
Grewal
Thomas
T
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*
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