Integrins make a choice

Signaling researchers have only a few factors with which to explain a whole lot of biology. On page 407, Goel et al. describe how two integrin variants channel the actions of a single factor, insulin-like growth factor (IGF), into two distinct pathways that induce either adhesion or proliferation.Figure IGF and integrins can collaborate in either adhesion or proliferation.The β1A integrin variant was known to be associated with proliferation and the β1C variant to inhibit it. IGF and its receptors had also been found to enhance adhesion through β1 integrins. Goel et al. find that, in cells with β1A integrin, IGF binding to its receptor induces formation of a ternary complex of integrin, IGF receptor and the downstream signaling protein IRS-1. The resultant boost in cell proliferation is, however, prevented by expression of the β1C integrin. A short insertion in the cytoplasmic tail of β1C brings in the Gab1 and Shp2 proteins, with the Shp2 phosphatase removing the phosphates that would otherwise have led to IRS-1 recruitment and signaling. The result is synergistic activation of adhesion by the IGF receptor and β1C integrin. It is not yet clear which molecular output the IGF receptor is bringing to the adhesion equation. But removal of β1C with a ribozyme prevents IGF-stimulated adhesion, and β1C addition to prostate tumor cells before their injection into host animals significantly reduces the size of the resultant tumors. ▪