Identification and characterization of LTBP-2, a novel latent transforming growth factor-beta-binding protein

Abstract

Latent transforming growth factor-beta (TGF-beta)-binding protein (LTBP) is a component of the latent TGF-beta complex in human platelets. LTBP is composed of two different cysteine-rich repeat sequences, i.e. epidermal growth factor (EGF)-like repeats and a repeat containing 8 cysteine residues. The overall structure of LTBP is similar to those of the microfibrillar proteins fibrillin-1 and fibrillin-2. Here we report the identification of a novel protein termed LTBP-2, which is structurally related to LTBP. cDNA for LTBP-2 was obtained from human foreskin fibroblast cDNA libraries using a fragment of the LTBP cDNA as a probe. LTBP-2 is composed of 20 EGF-like repeats and four copies of the 8-cysteine repeat. The amino acid sequence of LTBP-2 is 41% identical to that of LTBP and 25% identical to that of fibrillin-1. LTBP-2 is synthesized as a 240-kDa protein by human foreskin fibroblasts and also by COS cells transfected with the isolated LTBP-2 cDNA. Similar to LTBP, a considerable part of LTBP-2 was found to be associated with extracellular matrix. Co-transfection of cDNAs for LTBP-2 and TGF-beta 1 revealed that LTBP-2 forms a high molecular weight complex with the TGF-beta 1 precursor. The LTBP-2 gene was assigned to chromosome 14q24. These results indicate that different forms of latent TGF-beta complexes occur and suggest that the different associated proteins may function to target the complexes to specific sites.