Isolation of a novel latent transforming growth factor-beta binding protein gene (LTBP-3).
This paper reports the molecular cloning of a novel gene in the mouse that shows structural similarities to the microfibril protein fibrillin and to the latent transforming growth factor-beta (TGF-beta) binding protein (LTBP), a component of the latent TGF-beta complex. The gene was initially isolated during a low stringency polymerase chain reaction screen of a NIH 3T3 cell cDNA library using primers that amplify a human fibrillin-1 epidermal growth factor-like repeat. Three lines of evidence suggest that the mouse gene is a third member of the LTBP gene family, which we designate LTBP-3. First, the deduced polypeptide, which consists of 15 epidermal growth factor-like repeats, 3 TGF binding protein repeats, and 2 proline- and glycine-rich sequences, shows 38.4% identity with LTBP-1 but only 27% identity with fibrillin-1. Second, the gene appears to be co-expressed in developing mouse tissues with TGF-beta. Third, immunoprecipitation studies using mouse preosteoblast MC3T3-E1 cells and a specific anti-peptide polyclonal antiserum reveal that the mouse polypeptide forms a complex with the TGF-beta 1 precursor. Finally, we note that the LTBP-3 gene was recently localized to a distinct genetic locus (Li, X., Yin, W., Perez-Jurado, L., Bonadio, J., and Francke, U. (1995) Mamm. Genome 6, 42-45). Identification of a third binding protein provides further insight into a mechanism by which latent TGF-beta complexes can be targeted to connective tissue matrices and cells.
Yin
W
W
Department of Pathology, University of Michigan, Ann Arbor 48109-0650, USA.
Smiley
E
E
Germiller
J
J
Mecham
R P
RP
Florer
J B
JB
Wenstrup
R J
RJ
Bonadio
J
J
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary; D000071838:Fibrillin-1; D000071837:Fibrillins; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D053779:Latent TGF-beta Binding Proteins; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D054392:Adipokines
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018076:DNA, Complementary; D000071838:Fibrillin-1; D000071837:Fibrillins; D053779:Latent TGF-beta Binding Proteins; D008840:Microfilament Proteins; D016212:Transforming Growth Factor beta; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse; C509032:LTBP1 protein, human; C509038:LTBP3 protein, human; C509033:Ltbp1 protein, mouse; C509039:Ltbp3 protein, mouse