HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 286/5/L1016    most recent 00356.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Siddiqui, S. S. Articles by Malik, A. B. Search for Related Content PubMed PubMed Citation Articles by Siddiqui, S. S. Articles by Malik, A. B.

Albumin endocytosis in endothelial cells induces TGF- receptor II signaling

Department of Pharmacology, College of Medicine, University of Illinois, Chicago, Illinois 60612

Submitted 9 December 2003 ; accepted in final form 30 December 2003

Vascular endothelial cells undergo albumin endocytosis using a set of albumin binding proteins. This process is important for maintaining cellular homeostasis. We showed by several criteria that the previously described 73-kDa endothelial cell surface albumin binding protein is the 75-kDa transforming growth factor (TGF)- receptor type II (TRII). Albumin coimmunoprecipitated with TRII from a membrane fraction from rat lung microvascular endothelial cells. Albumin endocytosis-negative COS-7 cells became albumin endocytosis competent when transfected with wild-type TRII but not when transfected with a domain-negative kinase mutant of TRII. An antibody specific for TRII inhibited albumin endocytosis. A mink lung epithelial cell line, which expresses both the TGF- receptor type I (TRI) and the TRII receptor, exhibited albumin binding to the cell surface and endocytosis. In contrast, mutant L-17 and DR-26 cells lacking TRI or TRII, respectively, each showed a dramatic reduction in binding and endocytosis. Albumin endocytosis induced Smad2 phosphorylation and Smad4 translocation as well as increased protein expression of the inhibitory Smad, Smad7. We identified regions of significant homology between amino acid sequences of albumin and TGF-, suggesting a structural basis for the interaction of albumin with the TGF- receptors and subsequent activation of TRII signaling. The observed albumin-induced internalization of TRII signaling may be an important mechanism in the vessel wall for controlling TGF- responses in endothelial cells.

albumin-transforming growth factor- sequence identity; transforming growth factor- receptor II complimentary deoxyribonucleic acid; Smad2; Smad4; Smad7

This article has been cited by other articles:

				R. Diwakar, A. L. Pearson, P. Colville-Nash, N. J. Brunskill, and M. E. C. Dockrell The role played by endocytosis in albumin-induced secretion of TGF-beta1 by proximal tubular epithelial cells Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1464 - F1470. [Abstract] [Full Text] [PDF]

				S. Ivens, D. Kaufer, L. P Flores, I. Bechmann, D. Zumsteg, O. Tomkins, E. Seiffert, U. Heinemann, and A. Friedman TGF-{beta} receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis Brain, February 1, 2007; 130(2): 535 - 547. [Abstract] [Full Text] [PDF]

				S. S. Siddiqui, Z. K. Siddiqui, S. Uddin, R. D. Minshall, and A. B. Malik p38 MAPK activation coupled to endocytosis is a determinant of endothelial monolayer integrity Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L114 - L124. [Abstract] [Full Text] [PDF]

				T. A. John, B. O. Ibe, and J. Usha Raj Oxygen alters caveolin-1 and nitric oxide synthase-3 functions in ovine fetal and neonatal lung microvascular endothelial cells Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L1079 - L1093. [Abstract] [Full Text] [PDF]

				D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF]