PHAS-I PHOSPHORYLATION IN RESPONSE TO FETAL BOVINE SERUM (FBS) IS REGULATED BY AN ERK1 ERK2-INDEPENDENT AND RAPAMYCIN-SENSITIVE PATHWAY IN 3T3-L1 ADIPOCYTES/

The phosphorylation state of PHAS-I is thought to be important in the regulation of protein synthesis initiation, PHAS-I phosphorylation sig nificantly increases in response to growth factors and insulin, ERK1/E RK2 have previously been implicated as PHAS-I kinases, Present work ut ilised a specific phosphorothioate oligonucleotide antisense strategy against ERK1/ERK2 to determine whether ERK1/ERK2 mediate FBS-stimulate d PHAS-I phosphorylation in vivo. Depleting > 90% of cellular ERK1/ERK 2 had no effect on FES-stimulated PHAS-I phosphorylation. However, tre atment of cells with a specific p70(S6k) pathway inhibitor, rapamycin, markedly attenuated FBS-stimulated PHAS-I phosphorylation. These resu lts indicate that PHAS-I phosphorylation in response to FBS occurs thr ough an ERK1/ERK2-independent and rapamycin-sensitive pathway in 3T3-L 1 adipocytes. (C) 1997 Federation of European Biochemical Societies.