title: Fibroblast growth factor-1-inducible gene FR-17 encodes a nonmuscle alpha-actinin isoform.
abstract: Polypeptide growth factor binding to cell surface receptors activates a cytoplasmic signaling cascade that ultimately promotes the expression of specific nuclear genes. As an approach to investigate the molecular mechanism of fibroblast growth factor (FGF)-1 mitogenic signaling, we have begun to identify and characterize FGF-1-inducible genes in murine NIH 3T3 cells. Here we report that one of these genes, termed FGF-regulated (FR)-17, is predicted to encode a nonmuscle isoform of alpha-actinin, an actin cross-linking protein found along microfilaments and in focal adhesion plaques. FGF-1 induction of alpha-actinin mRNA expression is first detectable at 2 h after mitogen addition and is dependent on the novo RNA and protein synthesis. Maximal alpha-actinin mRNA expression, corresponding to an approximately nineteenfold level of induction, is present after 12 h of FGF-1 stimulation. Western blot analysis 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, and the tumor promoter phorbol myristate acetate can also induce alpha-actinin mRNA expression. Finally, nonmuscle alpha-actinin mRNA is expressed in vivo in a tissue-specific manner, with relatively high levels detected in adult mouse intestine and kidney. These results indicate that nonmuscle alpha-actinin is a serum-, polypeptide growth factor-, and tumor promoter-inducible gene in mouse fibroblasts.
authors.affiliation: Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Hsu
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: G F
authors.initials: GF
authors.lastname: Alberts
authors.forename: K A
authors.initials: KA
authors.lastname: Peifley
authors.forename: J A
authors.initials: JA
authors.lastname: Winkles
mesh_terms: D016475:3T3 Cells / Q000166:cytology / Q000502:physiology; D000185:Actinin / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D007536:Isomerism; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D017386:Sequence Homology, Amino Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001798:Blood Proteins; D018076:DNA, Complementary; D006133:Growth Substances; D012333:RNA, Messenger; D016220:Fibroblast Growth Factor 1; D000185:Actinin; D013755:Tetradecanoylphorbol Acetate