High density lipoprotein-induced signaling of the MAPK pathway involves scavenger receptor type BI-mediated activation of Ras.
High density lipoprotein (HDL) stimulates multiple signaling pathways. HDL-induced activation of the mitogen-activated protein kinase (MAPK) pathway can be mediated by protein kinase C (PKC) and/or pertussis toxin-sensitive G-proteins. Although HDL-induced activation of MAPK involves Raf-1, Mek, and Erk1/2, the upstream contribution of p21(ras) (Ras) on the activation of Raf-1 and MAPK remains elusive. Here we examine the effect of HDL on Ras activity and demonstrate that HDL induces PKC-independent activation of Ras that is completely blocked by pertussis toxin, thus implicating heterotrimeric G-proteins. In addition, the HDL-induced activation of Ras is inhibited by a neutralizing antibody against scavenger receptor type BI. We conclude that the binding of HDL to scavenger receptor type BI activates Ras in a PKC-independent manner with subsequent induction of the MAPK signaling cascade.
Grewal
Thomas
T
Departament de Biologia Cellular, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain.
de Diego
Iñaki
I
Kirchhoff
Matthias F
MF
Tebar
Francesc
F
Heeren
Joerg
J
Rinninger
Franz
F
Enrich
Carlos
C
D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D015398:Signal Transduction / Q000187:drug effects*; D018631:ras Proteins / Q000378:metabolism*
D018955:CD36 Antigens; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D018631:ras Proteins