Identification of two isoforms of the Cak receptor kinase that are coexpressed in breast tumor cell lines

Abstract

The Cak receptor kinase is a member of a novel family of receptors that are characterized by the unique structure of the ectodomains. We have identified a new isoform of Cak that differs from the original isolate by the deletion of 37 amino acids in the cytoplasmic juxtamembrane sequence. Analysis of the genomic sequence suggests that the two isoforms arise by exon skipping. The isoform-specific insert contains the motif NPXY, which was previously shown to be involved in diverse signaling function in a number of receptors. By RNase protection analyses, we found that the long isoform, Cak I is expressed at three- to sevenfold the abundance of the short isoform (Cak II). By Western blotting, Cak I receptor was found to be expressed in mouse embryos and in adult brain. Cak II protein was not detected in mouse embryos or adult tissues, but is abundantly expressed in some breast tumor cell lines. The expression profile of Cak suggests that its primary function is likely to be in developmental regulation. The coexpression of the Cak isoforms in some epithelial cell lines suggests that heterodimer formation may be a key feature in the function of the receptor.