An alternatively spliced fibroblast growth factor (FGF)-5 mRNA is abundant in brain and translates into a partial agonist/antagonist for FGF-5 neurotrophic activity.

K Ozawa; S Suzuki; M Asada; Y Tomooka; A J Li; A Yoneda; A Komi; T Imamura

An alternatively spliced fibroblast growth factor (FGF)-5 mRNA is abundant in brain and translates into a partial agonist/antagonist for FGF-5 neurotrophic activity.

K Ozawa, S Suzuki, M Asada, Y Tomooka, A J Li, A Yoneda, A Komi, T Imamura

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

35 Citationer (Scopus)

Abstract

Udgivelsesdato: 1998-Oct-30

Originalsprog	Engelsk
Tidsskrift	Journal of Biological Chemistry
Vol/bind	273
Udgave nummer	44
Sider (fra-til)	29262-71
Antal sider	9
ISSN	0021-9258
Status	Udgivet - 1998
Udgivet eksternt	Ja

Bibliografisk note

Keywords: Alternative Splicing; Amino Acid Sequence; Animals; Base Sequence; Brain; Cell Differentiation; Cloning, Molecular; DNA, Complementary; Escherichia coli; Fibroblast Growth Factor 5; Fibroblast Growth Factors; Humans; Mice; Molecular Sequence Data; PC12 Cells; Protein Binding; RNA, Messenger; Rats; Receptors, Fibroblast Growth Factor; Recombinant Proteins; Ribonucleases

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Citationsformater

@article{9e169f205ee411dd8d9f000ea68e967b,

title = "An alternatively spliced fibroblast growth factor (FGF)-5 mRNA is abundant in brain and translates into a partial agonist/antagonist for FGF-5 neurotrophic activity.",

abstract = "We detected in the brain and then cloned two novel, short forms of human and mouse fibroblast growth factor (FGF)-5 mRNA, which were designated human FGF-5S (hFGF-5S) and mouse FGF-5S (mFGF-5S), respectively. Genomic analysis indicated that mFGF-5S and authentic mFGF-5 mRNAs were transcribed from a single gene; hFGF-5S and mFGF-5S mRNAs were generated by excluding the second exon of the respective FGF-5 genes, and the alternatively spliced mRNAs encoded for 123- and 121-amino acid proteins, respectively. Indeed, a neuron-like cell line expressing mFGF-5S mRNA secreted a protein of the expected size and with FGF-5 antigenicity. In PC12 cells, expression of hFGF-5 or exposure to hFGF-5 protein induced differentiation. Neither expression of hFGF-5S, alone, nor co-expression of hFGF-5S with hFGF-5 induced significant differentiation. At high concentrations, hFGF-5S protein partially antagonized FGF-5 activity, whereas by itself, hFGF-5S exerted very weak neurotrophic activity. hFGF-5S protein binds to FGF receptor (FGFR)-1 on PC12 transfectants and partially inhibits hFGF-5-induced tyrosine phosphorylation of FGFR-1 and an FGFR substrate, but it also induces phosphorylation by itself. These results suggest that FGF-5S is a naturally expressed partial agonist/antagonist of FGF-5 neurotrophic activity in the brain and that its effects are exerted in part at the level of the receptor.",

author = "K Ozawa and S Suzuki and M Asada and Y Tomooka and Li, {A J} and A Yoneda and A Komi and T Imamura",

note = "Keywords: Alternative Splicing; Amino Acid Sequence; Animals; Base Sequence; Brain; Cell Differentiation; Cloning, Molecular; DNA, Complementary; Escherichia coli; Fibroblast Growth Factor 5; Fibroblast Growth Factors; Humans; Mice; Molecular Sequence Data; PC12 Cells; Protein Binding; RNA, Messenger; Rats; Receptors, Fibroblast Growth Factor; Recombinant Proteins; Ribonucleases",

year = "1998",

language = "English",

volume = "273",

pages = "29262--71",

journal = "Journal of Biological Chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology, Inc.",

number = "44",

}

TY - JOUR

T1 - An alternatively spliced fibroblast growth factor (FGF)-5 mRNA is abundant in brain and translates into a partial agonist/antagonist for FGF-5 neurotrophic activity.

AU - Ozawa, K

AU - Suzuki, S

AU - Asada, M

AU - Tomooka, Y

AU - Li, A J

AU - Yoneda, A

AU - Komi, A

AU - Imamura, T

N1 - Keywords: Alternative Splicing; Amino Acid Sequence; Animals; Base Sequence; Brain; Cell Differentiation; Cloning, Molecular; DNA, Complementary; Escherichia coli; Fibroblast Growth Factor 5; Fibroblast Growth Factors; Humans; Mice; Molecular Sequence Data; PC12 Cells; Protein Binding; RNA, Messenger; Rats; Receptors, Fibroblast Growth Factor; Recombinant Proteins; Ribonucleases

PY - 1998

Y1 - 1998

N2 - We detected in the brain and then cloned two novel, short forms of human and mouse fibroblast growth factor (FGF)-5 mRNA, which were designated human FGF-5S (hFGF-5S) and mouse FGF-5S (mFGF-5S), respectively. Genomic analysis indicated that mFGF-5S and authentic mFGF-5 mRNAs were transcribed from a single gene; hFGF-5S and mFGF-5S mRNAs were generated by excluding the second exon of the respective FGF-5 genes, and the alternatively spliced mRNAs encoded for 123- and 121-amino acid proteins, respectively. Indeed, a neuron-like cell line expressing mFGF-5S mRNA secreted a protein of the expected size and with FGF-5 antigenicity. In PC12 cells, expression of hFGF-5 or exposure to hFGF-5 protein induced differentiation. Neither expression of hFGF-5S, alone, nor co-expression of hFGF-5S with hFGF-5 induced significant differentiation. At high concentrations, hFGF-5S protein partially antagonized FGF-5 activity, whereas by itself, hFGF-5S exerted very weak neurotrophic activity. hFGF-5S protein binds to FGF receptor (FGFR)-1 on PC12 transfectants and partially inhibits hFGF-5-induced tyrosine phosphorylation of FGFR-1 and an FGFR substrate, but it also induces phosphorylation by itself. These results suggest that FGF-5S is a naturally expressed partial agonist/antagonist of FGF-5 neurotrophic activity in the brain and that its effects are exerted in part at the level of the receptor.

AB - We detected in the brain and then cloned two novel, short forms of human and mouse fibroblast growth factor (FGF)-5 mRNA, which were designated human FGF-5S (hFGF-5S) and mouse FGF-5S (mFGF-5S), respectively. Genomic analysis indicated that mFGF-5S and authentic mFGF-5 mRNAs were transcribed from a single gene; hFGF-5S and mFGF-5S mRNAs were generated by excluding the second exon of the respective FGF-5 genes, and the alternatively spliced mRNAs encoded for 123- and 121-amino acid proteins, respectively. Indeed, a neuron-like cell line expressing mFGF-5S mRNA secreted a protein of the expected size and with FGF-5 antigenicity. In PC12 cells, expression of hFGF-5 or exposure to hFGF-5 protein induced differentiation. Neither expression of hFGF-5S, alone, nor co-expression of hFGF-5S with hFGF-5 induced significant differentiation. At high concentrations, hFGF-5S protein partially antagonized FGF-5 activity, whereas by itself, hFGF-5S exerted very weak neurotrophic activity. hFGF-5S protein binds to FGF receptor (FGFR)-1 on PC12 transfectants and partially inhibits hFGF-5-induced tyrosine phosphorylation of FGFR-1 and an FGFR substrate, but it also induces phosphorylation by itself. These results suggest that FGF-5S is a naturally expressed partial agonist/antagonist of FGF-5 neurotrophic activity in the brain and that its effects are exerted in part at the level of the receptor.

M3 - Journal article

C2 - 9786939

SN - 0021-9258

VL - 273

SP - 29262

EP - 29271

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 44

ER -