FIBROBLAST GROWTH FACTOR-1-INDUCIBLE GENE FR-17 ENCODES A NONMUSCLE ALPHA-ACTININ ISOFORM

Polypeptide growth factor binding to cell surface receptors activates a cytoplasmic signaling cascade that ultimately promotes the expressio n of specific nuclear genes. As an approach to investigate the molecul ar mechanism of fibroblast growth factor (FGF)-1 mitogenic signaling, we have begun to identify and characterize FGF-1-inducible genes in mu rine NIH 3T3 cells. Here we report that one of these genes, termed FGF -regulated (FR)-17, is predicted to encode a nonmuscle isoform of alph a-actinin, an actin cross-linking protein found along microfilaments a nd in focal adhesion plaques. FGF-1 induction of alpha-actinin mRNA ex pression is first detectable at 2 h after mitogen addition and is depe ndent on de novo RNA and protein synthesis. Maximal alpha-actinin mRNA expression, corresponding to an approximately nineteenfold level of i nduction, is present after 12 h of FGF-1 stimulation. Western blot ana lysis indicated that FGF-1-stimulated cells also produce an increased amount of alpha-actinin protein. The FGF-1-related mitogen FGF-2, calf serum, several of the polypeptide growth factors present in serum, an d the tumor promoter phorbol myristate acetate can also induce alpha-a ctinin mRNA expression. Finally, nonmuscle alpha-actinin mRNA is expre ssed in vivo in a tissue-specific manner, with relatively high levels detected in adult mouse intestine and kidney. These results indicate t hat nonmuscle alpha-actinin is a serum-, polypeptide growth factor-, a nd tumor promoter-inducible gene in mouse fibroblasts. (C) 1996 Wiley- Liss, Inc.