An MBoC Favorite: Fibronectin/integrin interaction induces tyrosine phosphorylation of a 120-kDa protein

Abstract

This paper marks the early stages of understanding the molecular mechanisms of intracellular signaling activated by the extracellular matrix (ECM). I like it also as an exploration of a new area through closely linked questions. By 1991, many integrins had been cloned and their ECM ligand specificities studied. A trio of papers from 1989 to 1990 reported that integrin occupancy could affect complex cell behaviors, such as differentiation; however, the mechanisms of these behaviors remained unknown. In separate research, phosphotyrosinecontaining proteins had been observed to be concentrated in focal adhesions. In this paper, Guan et al. (1991) linked these areas by demonstrating that fibroblast adhesion to fibronectin correlated with dynamic, environment-dependent, tyrosine phosphorylation of a 120-kDa protein. The results included important clues for future researchers: multiple domains of fibronectin were needed for the strongest effect, and the cytoplasmic domain of β1 integrin was also necessary. The 120-kDa protein was identified as focal adhesion kinase in 1992 publications from other laboratories. By identifying an intracellular biochemical event correlated with ECM–integrin interactions and adhesive functions, this paper presaged multiple top-cited MBoC papers of the 1990s.