Insulin elicits the tyrosine phosphorylation of one or more proteins of 160-185 kDa in many cell types. Peptide sequences, obtained from this protein purified from mouse 3T3-L1 adipocytes (pp160), were used as the basis for cloning its cDNA. pp160 is highly homologous to the insulin receptor substrate 1, previously cloned from rat liver. Thus, this component of the insulin signaling pathway is the same in adipocytes and in liver.