THE NEUROPEPTIDE-Y PEPTIDE YY Y1 RECEPTOR IS COUPLED TO, MAP KINASE VIA PKC AND RAS IN CHO CELLS

The neuropeptide Y/peptide YY (PYY) Y1 receptor subtype mediates proli ferative responses. This report identifies effector molecules which me diate mitogen-activated protein kinase (MAPK) phosphorylation by Y1 re ceptor activation in transfected CHO cells. Pertussis toxin pretreatme nt abolishes this effect, indicating involvement of G(i) or G(o) prote ins. Inhibition of protein kinase C (PKC) also blocks PYY-induced MAPK phosphorylation. Additionally in this cell model PYY causes an increa se in GTP binding to Ras protein, and co transfection of dominant nega tive constructs for Ras and Raf blocks PW effects on MAPK. These data suggest a novel mechanism for Y1 receptor coupling to MAPK, which is a t once pertussis toxin-sensitive as well as PKC and Ras-dependent. (C) 1998 Academic Press.