TRITON X-100-RESISTANT MEMBRANE COMPLEXES FROM CULTURED KIDNEY EPITHELIAL-CELLS CONTAIN THE SRC FAMILY PROTEIN-TYROSINE KINASE P62(YES)

We have previously isolated detergent-resistant membrane complexes fro m lysates of cultured kidney epithelial cells. These structures are en riched in proteins anchored by glycosylphosphatidylinositol, which are localized to the apical plasma membrane of epithelial cells, and have a distinctive lipid composition. We now report that the membranes con tain p62(yes), a non-receptor tyrosine kinase of the Src family. p62(y es) is the only major tyrosine-phosphorylated protein in the membrane complexes when they are isolated. Several proteins in the complexes ca n serve as substrates for phosphorylation by p62(yes) in vitro. The ki nase is enriched at least 10-fold in the insoluble membranes compared to cellular membranes. p60(c-src) and p60(v-src), which are highly hom ologous to p62(yes), are not present in the complexes, even when the m embranes are isolated from cells that overexpress the proteins. As p62 (yes) is located near the apical plasma membrane of epithelial cells i n several tissues in vivo, interaction of the kinase with other compon ents of a detergent-resistant membrane microdomain may play an importa nt role in transmembrane signal transduction.