LOSS OF A CONSENSUS HEPARIN-BINDING SITE BY ALTERNATIVE SPLICING OF LATENT TRANSFORMING-GROWTH-FACTOR-BETA BINDING PROTEIN-1

Latent transforming growth factor-beta binding protein-1 (LTBP-1), pla ys an important role in controlling localisation and activation of tra nsforming growth factor-beta (TGF-beta). We show that alternative spli cing generates a form of mRNA which lacks bases 1277-1435 (termed LTBP -1 Delta 53). The 53 amino acids encoded by these bases include the ei ghth cysteine of the first cysteine repeat and a consensus heparin bin ding sequence. Sequencing of genomic clones showed that alternative sp licing resulted from the use of an intra-exonic 3' splice acceptor sit e. The loss of the heparin binding site implies that LTBP-1 Delta 53 w ill bind to the extracellular matrix less efficiently than LTBP-1. (C) 1998 Federation of European Biochemical Societies.