Identification of an atypical lipoprotein‐binding protein from human aortic smooth muscle as T‐cadherin

Abstract

We have previously described an atypical lipoproteinbinding protein of about 105 kDa (p105) in membranes of vascular smooth muscle cells (VSMCs) that is distinct from currently known lipoprotein receptors. In the present work we have developed a procedure for purification of p105 from human aortic media. Partial sequencing of purified protein has revealed identity of p105 with human T-cadherin. Anti-peptide antisera raised against human T-cadherin recognized a protein spot corresponding to the purified p105 on two-dimensional Western blots. The antisera also inhibited LDL binding to p105 on ligand blots. We conclude that the 105 kDa lipoprotein-binding protein present in human VSMCs is T-cadherin, an unusual glycosylphosphatidylinositol-anchored member of the cadherin family of cell-cell adhesion proteins.z 1998 Federation of European Biochemical Societies.

Identification of T-cadherin as a Novel Target of DNA Methyltransferase 3B and Its Role in the Suppression of Nerve Growth Factor-mediated Neurite Outgrowth in PC12 Cells

“…T-Cad is co-segregated with signaling molecules such as G-protein and SRC family kinase, which implicates its role as an intracellular signaling molecule (25). Interestingly, T-Cad can also function as a receptor for low density lipoprotein and adiponection/Acrp30 (26,27). T-Cad is down-regulated by growth factors such as IGF, EGF, and bDGF in smooth muscle cells (28).…”

The Glycosyl Phosphatidylinositol Anchor of Human T-Cadherin Binds Lipoproteins

“…The co-localization of AS 161-179 immunoreactivity (Fig. 2C) and LDL-binding ( (11,12). Immunoblots were sequentially incubated with anti-T-cad peptide antisera (or rabbit serum as the nonspecific control) and secondary horseradish peroxidase-conjugated anti-rabbit IgG.…”

“…LDL-binding to T-cad is inhibited when samples are heated in the presence of ␤-mercaptoethanol prior to SDS-PAGE (12,16). These effects were interpreted as consequences of structural perturbances of the lipoprotein binding domain(s) (e.g., reduction of relevant disulfide bonds), and suggested some remote analogy with the LDL receptor family.…”

“…Using this ligand blotting technique we identified two vascular smooth muscle cell (SMC) proteins with apparent molecular masses of 105 kDa (p105) and 130 kDa (p130) that bind native LDL, modified LDL's and VLDL (15)(16)(17). Amino acid sequencing of tryptic fragments of protein purified from human aortic medial tissue and immunoblot analysis of purified proteins indicated that p105 is identical with mature human T-cad (12) and that p130 is identical with the unprocessed T-cad precursor (11). In HEK293 cells stably transfected with human T-cad cDNA a colocalization of LDL-binding and anti-T-cad immunoreactivity to the expected mature (105 kDa) and precursor (130 kDa) forms of T-cad was shown (18).…”

T-cadherin Is Essential for Adiponectin-mediated Revascularization*

“…It is now appreciated that T-cadherin has functions that extend beyond the typical cadherin behavior of cellto-cell adhesion. T-cadherin is highly expressed in the vasculature including endothelial cells (24), smooth muscle cells (25), and pericytes (26). It has been implicated in modulation of angiogenic activities in cultured endothelial cells; however, some studies report that it promotes angiogenesis (27)(28)(29)(30)(31), whereas others report its attenuation (32,33).…”