We have examined the mechanism of signal transduction by the hemidesmosomal integrin α6β4, a laminin receptor involved in morphogenesis and tumor progression. Immunoprecipitation and immune complex kinase assays indicated that antibody- or laminin-induced ligation of α6β4 causes tyrosine phosphorylation of the β4 subunit in intact cells and that this event is mediated by a protein kinase(s) physically associated with the integrin. Co-immunoprecipitation and GST fusion protein binding experiments showed that the adaptor protein She forms a complex with the tyrosine-phosphorylated β4 subunit. She is then phosphorylated on tyrosine residues and recruits the adaptor Grb2, thereby potentially linking α6β4 to the ras pathway. The β4 subunit was found to be phosphorylated at multiple tyrosine residues in vivo, including a tyrosine-based activation motif (TAM) resembling those found in T and B cell receptors. Phenylalanine substitutions at the β4 TAM disrupted association of α6β4 with hemidesmosomes, but did not interfere with tyrosine phosphorylation of She and recruitment of Grb2. These results indicate that signal transduction by the α6β4 integrin is mediated by an associated tyrosine kinase and that phosphorylation of distinct sites in the β4 tail mediates assembly of the hemidesmosomal cytoskeleton and recruitment of Shc/Grb2.
|Number of pages||12|
|Publication status||Published - 1995|
- Tyrosine phosphorylation
ASJC Scopus subject areas
- Cell Biology