Alternative splicing of LTBP-3.
LTBPs bind the 100-kDa latent TGF-beta complex and thereby regulate TGF-beta assembly, tissue localization, and function. However, the 100-kDa complex is not always associated with LTBP, and, conversely, evidence suggests that LTBP has a distinct role in the extracellular matrix. As yet, there are no data to explain how the binding interaction between LTBP and the 100-kDa complex is regulated. This report provides the first direct evidence of alternative splicing of an LTBP gene. Two alternative splice sites in the mouse LTBP-3 gene have been identified based on in vivo and in vitro studies. Alternative splicing at one site in particular was found to disrupt a structural motif involved in the binding interaction with the 100-kDa latent TGF-beta complex. Therefore, alternative splicing may represent a molecular mechanism by which the uncomplexed form of LTBP-3 is produced, and, as a corollary, by which the 100-kDa latent TGF-beta 1 complex is produced.
Yin
W
W
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0417, USA.
Smiley
E
E
Bonadio
J
J
D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D003001:Cloning, Molecular; D005091:Exons / Q000235:genetics; D007438:Introns / Q000235:genetics; D053779:Latent TGF-beta Binding Proteins; D051379:Mice; D008969:Molecular Sequence Data; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D014162:Transfection / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D053779:Latent TGF-beta Binding Proteins; C509039:Ltbp3 protein, mouse; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta