Prostaglandin F-2 alpha (PGrF(2 alpha)), a mitogen for Swiss 3T3 cells, triggers cyclin D1 mRNA/protein expression prior to cellular entry into the S phase, but fails to raise cdk4 or cyclin D3 levels, while 1-oleoyl-2-diacylglycerol (OAG), a protein kinase C (PKC) and tyrosine kinase (TK) activator, induces only cyclin D1 expression with no mitogenic response. In contrast, in PKC-depleted or -inhibited cells, PGF(2 alpha), but not OAG, increases cyclin D1 expression with no mitogenic response. Finally, OAG, in the presence of orthovanadate (Na3VO4) or TGF(beta 1), induces DNA synthesis. Thus, it appears that PGF(2 alpha) triggers cyclin D1 expression via two independent signaling events that complement with TGF(beta 1)-triggered events to induce DNA synthesis.