THE CYTOPLASMIC TYROSINE KINASE FER TS ASSOCIATED WITH THE CATENIN-LIKE SUBSTRATE PP120 AND IS ACTIVATED BY GROWTH-FACTORS

The FER gene encodes a cytoplasmic tyrosine kinase with a single SH2 d omain and an extensive amino terminus. In order to understand the cell ular function of the FER kinase, we analyzed the effect of growth fact or stimulation on the phosphorylation and activity of FER. Stimulation of A431 cells and 3T3 fibroblasts with epidermal growth factor or pla telet-derived growth factor results in the phosphorylation of FER and two associated polypeptides. The associated polypeptides were shown to be the epidermal growth factor receptor or the platelet-derived growt h factor receptor and a previously identified target, pp120. Since pp1 20 had previously been shown to interact with components of the cadher in-catenin complex, these results implicate FER in the regulation of c ell-cell interactions. The physical association of FER with pp120 was found to be constitutive and was mediated by a 400-amino-acid sequence in the amino terminus of FER. Analyses of that sequence revealed that it has the ability to form coiled coils and that it oligomerizes in v itro. The identification of a coiled coil sequence in the FER kinase a nd the demonstration that the sequence mediates association with a pot ential substrate suggest a novel mechanism for signal transduction by cytoplasmic tyrosine kinases.