The latent transforming growth factor beta binding protein (LTBP) family

Biochem J. 2000 Dec 15;352 Pt 3(Pt 3):601-10.

Abstract

The transforming growth factor beta (TGFbeta) cytokines are a multi-functional family that exert a wide variety of effects on both normal and transformed mammalian cells. The secretion and activation of TGFbetas is regulated by their association with latency-associated proteins and latent TGFbeta binding proteins (LTBPs). Over the past few years, three members of the LTBP family have been identified, in addition to the protoype LTBP1 first sequenced in 1990. Three of the LTBP family are expressed in a variety of isoforms as a consequence of alternative splicing. This review summarizes the differences between the isoforms in terms of the effects on domain structure and hence possible function. The close identity between LTBPs and members of the fibrillin family, mutations in which have been linked directly to Marfan's syndrome, suggests that anomalous expression of LTBPs may be associated with disease. Recent data indicating that differential expression of LTBP1 isoforms occurs during the development of coronary heart disease is considered, together with evidence that modulation of LTBP function, and hence of TGFbeta activity, is associated with a variety of cancers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing / genetics
  • Animals
  • Arteriosclerosis / metabolism
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Latent TGF-beta Binding Proteins
  • Multigene Family*
  • Neoplasms / metabolism
  • Organ Specificity
  • Transforming Growth Factor beta / physiology

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • LTBP1 protein, human
  • Latent TGF-beta Binding Proteins
  • Transforming Growth Factor beta