Endoglin Structure and Function: Determinants of Endoglin Phosphorylation by Transforming Growth Factor-beta Receptors.
From: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine 04074, USA.
The Journal of biological chemistry
- Publish Date: Sep 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 35
- Pages: 25110-23
- Medium: Print
- Language: English
- Citation (JAMA): Koleva Rositsa I, Conley Barbara A, Romero Diana, et al. Endoglin Structure and Function: Determinants of Endoglin Phosphorylation by Transforming Growth Factor-beta Receptors.. J. Biol. Chem. Sep 2006;281:25110-23
Abstract
Determination of the functional relationship between the transforming growth factor-beta (TGFbeta) receptor proteins endoglin and ALK1 is essential to the understanding of the human vascular disease, hereditary hemorrhagic telangiectasia. TGFbeta1 caused recruitment of ALK1 into a complex with endoglin in human umbilical vein endothelial cells (HUVECs). Therefore, we examined TGFbeta receptor-dependent phosphorylation of endoglin by the constitutively active forms of the TGFbeta type I receptors ALK1, ALK5, and the TGFbeta type II receptor, TbetaRII. Of these receptors, TbetaRII preferentially phosphorylated endoglin on cytosolic domain serine residues Ser(634) and Ser(635). Removal of the carboxyl-terminal tripeptide of endoglin, which comprises a putative PDZ-liganding motif, dramatically increased endoglin serine phosphorylation by all three receptors, suggesting that the PDZ-liganding motif is important for the regulation of endoglin phosphorylation. Constitutively active (ca)ALK1, but not caALK5, phosphorylated endoglin on cytosolic domain threonine residues. caALK1-mediated threonine phosphorylation required prior serine phosphorylation, suggesting a sequential mechanism of endoglin phosphorylation. Wild-type, but not a threonine phosphorylation-defective endoglin mutant blocked cell detachment and the antiproliferative effects of caALK1 expressed in HUVECs. These results suggest that ALK1 is a preferred TGFbeta receptor kinase for endoglin threonine phosphorylation in HUVECs and indicate a role for endoglin phosphorylation in the regulation of endothelial cell adhesion and growth by ALK1.
Mesh Headings (Keywords): Activin Receptors, Type II, Amino Acid Sequence, Antigens, CD, Cells, Cultured, Cytosol, Endothelium, Vascular, Humans, Molecular Sequence Data, Phosphorylation, Protein Structure, Tertiary, Receptors, Cell Surface, Receptors, Transforming Growth Factor beta, Sequence Homology, Amino Acid, Structure-Activity Relationship, Umbilical Veins
Check for Full Text / PubMed Unique Identifier (PMID): 16785228
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.