Loss of a consensus heparin binding site by alternative splicing of latent transforming growth factor-β binding protein-1

Abstract

Latent transforming growth factor-β binding protein-1 (LTBP-1), plays an important role in controlling localisation and activation of transforming growth factor-β (TGF-β). We show that alternative splicing generates a form of mRNA which lacks bases 1277–1435 (termed LTBP-1Δ53). The 53 amino acids encoded by these bases include the eighth cysteine of the first cysteine repeat and a consensus heparin binding sequence. Sequencing of genomic clones showed that alternative splicing resulted from the use of an intra-exonic 3′ splice acceptor site. The loss of the heparin binding site implies that LTBP-1Δ53 will bind to the extracellular matrix less efficiently than LTBP-1.