Molecular and functional aspects of latent transforming growth factor-β binding protein: just a masking protein?

Abstract

Latent transforming growth factor-beta (TGFbeta) binding protein (LTBP), a component of the high-molecular-weight latent TGFbeta complex, is found in various cell and tissue types. Originally described as a TGFbeta-masking protein, recent detections of four isoforms and numerous splice variants provide new aspects of its putative functional role. Regulation and sequestration of TGFbeta activity and structural remodeling of the extracellular matrix (ECM) seem to be the main tasks, but other possible functions might exist. The mechanism by which LTBP interacts with cell surface molecules or cellular receptors and ECM components remains unclear. Cellular, molecular and functional aspects will be discussed.

TGF-β1 and TGF-β2 expression after traumatic human spinal cord injury

“…The detection of TGF-b1 immunoreactivity that was associated with the endothelium of blood vessel walls probably reflects attachment of the cytokine to extracellular matrix proteins and might play a role in the retention, delivery and clearance of the cytokine. 17,18 Expression of TGF-b1 and TGF-b2 at the lesion site after traumatic SCI The present data show a rapid and dramatic induction of TGF-b1 immunoreactivity, both extracellularly and intracellularly (that is, in macrophages, astrocytes and neurons) supporting the suggestion that it plays a role in the early inflammatory reaction cascade following traumatic injury to the human spinal cord. This expression pattern is in line with experimental studies revealing an early and maintained increase of TGF-b at the mRNA and protein levels following experimental crush and contusion injuries of the adult rat spinal cord.…”

Transforming Growth Factor Beta in the Central Nervous System

“…There are four mammalian LTBP isoforms encoded by distinct genes, including LTBP-1, -2, -3, and -4 and different splice variants for each of them (Mangasser-Stephan & Gressner, 1999;Oklu & Hesketh, 2000). The significance of this structural diversity is mostly unclear at present.…”

Expression and matrix deposition of latent transforming growth factor β binding proteins in normal and fibrotic rat liver and transdifferentiating hepatic stellate cells in culture

“…6 The major component of this complex consists of a large glycoprotein (molecular weight, 125 to 210 kd) with a multidomain structure, designated LTBP, of which 4 isoforms and several splice variants have been characterized so far. [7][8][9][10][11][12][13] The formation of the large latent TGF-␤ complex includes covalent binding of the 3rd 8-cysteine repeat of LTBP-1, -3, and -4 to the aminoterminal portion of the TGF-␤ precursor, 14 termed latencyassociated peptide (LAP; molecular weight, 75 kd). The latter component noncovalently encompasses the active, C-terminal part of the TGF-␤ precursor molecule, i.e., the mature TGF-␤.…”