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 lipoprotein (LDL) binding proteins of M(r)105 and M(r)130 (p105 and p130) which have been putatively identified as the cell adhesion glycoprotein T-cadherin. Using cultured human and rat aortic SMC and analysis by ligand (LDL)- and immuno-blotting techniques we now confirm identity of p105 and p130 as T-cadherin, as adjudged by sensitivity to PI-PLC cleavage, 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, and bFGF, but not by vasoactive peptide hormones (angiotensin II, vasopressin, 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 quiescent 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 unaffected by phorbol ester, calcium ionophores, or calcium antagonists. The findings are compatible with a function for the lipoprotein binding proteins (T-cadherin) in negative regulation of SMC growth.
Kuzmenko
Y S
YS
Department of Research, Basel University Hospital, Switzerland.
Stambolsky
D
D
Kern
F
F
Bochkov
V N
VN
Tkachuk
V A
VA
Resink
T J
TJ
D000818:Animals; D015820:Cadherins / Q000302:isolation & purification / Q000378:metabolism*; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006131:Growth Inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D015820:Cadherins; D002352:Carrier Proteins; D006131:Growth Inhibitors; D006133:Growth Substances; C099972:H-cadherin; D008077:Lipoproteins, LDL; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta