CHARACTERISTICS OF SMOOTH-MUSCLE CELL LIPOPROTEIN BINDING-PROTEINS (P105 P130) AS T-CADHERIN AND REGULATION BY POSITIVE AND NEGATIVE GROWTH-REGULATORS/

Smooth muscle cells (SMC) express atypical surface low density lipopro tein (LDL) binding proteins of M(r)105 and M(r)130 (p105 and p130) whi ch have been putatively identified as the cell adhesion glycoprotein T -cadherin. Using cultured human and rat aortic SMC and analysis by lig and (LDL)- and immune-blotting techniques we now confirm identity of p 105 and p130 as T-cadherin, as adjudged by sensitivity to PI-PLC cleav age, insensitivity to trypsin degradation in the presence of calcium, and immunoreactivity to anti-T-cadherin peptide antisera. The function of T-cadherin (p105/p130) in the vasculature is unknown. The proteins were downmodulated by the peptide growth factors PDGF-BB, IGF, EGF, a nd bFGF, but not by vasoactive peptide hormones (angiotensin II, vasop ressin, bradykinin, and endothelin). TGF beta, a recognized inhibitor of SMC proliferation, per se had no effect but inhibited growth factor -induced p105/p130 downmodulation. Expression of p105/p130 in quiescen t SMC and growth-stimulated SMC (respectively, in serum-free and serum or PDGF-BB containing culture conditions) was increased by forskolin and 8-Br-cyclic GMP, both anti-mitogenic substances, but was unaffecte d by phorbol ester, calcium ionophores, or calcium antagonists. The fi ndings are compatible with a function for the lipoprotein binding prot eins (T-cadherin) in negative regulation of SMC growth. (C) 1998 Acade mic Press.