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Blood, 15 January 2005, Vol. 105, No. 2, pp. 670-678. Prepublished online as a Blood First Edition Paper on September 16, 2004; DOI 10.1182/blood-2004-04-1569. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1569v1 105/2/670    most recent 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 PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Maik-Rachline, G. Articles by Seger, R. Search for Related Content PubMed PubMed Citation Articles by Maik-Rachline, G. Articles by Seger, R. Related Collections Hemostasis, Thrombosis, and Vascular Biology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Extracellular phosphorylation converts pigment epithelium–derived factor from a neurotrophic to an antiangiogenic factor Galia Maik-Rachline, Shmuel Shaltiel, and Rony Seger From the Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel. The pigment epithelium–derived factor (PEDF) belongs to the superfamily of serine protease inhibitors (serpin). There have been 2 distinct functions attributed to this factor, which can act either as a neurotrophic or as an antiangiogenic factor. Besides its localization in the eye, PEDF was recently reported to be present also in human plasma. We found that PEDF purified from plasma is a phosphoprotein, which is extracellularly phosphorylated by protein kinase CK2 (CK2) and to a lesser degree, intracellularly, by protein kinase A (PKA). CK2 phosphorylates PEDF on 2 main residues, Ser24 and Ser114, and PKA phosphorylates PEDF on one residue only, Ser227. The physiologic relevance of these phosphorylations was determined using phosphorylation site mutants. We found that both CK2 and PKA phosphorylations of PEDF markedly affect its physiologic function. The fully CK2 phosphorylation site mutant S24, 114E abolished PEDF neurotrophic activity but enhanced its antiangiogenic activity, while the PKA phosphorylation site mutant S227E reduced PEDF antiangiogenic activity. This is a novel role of extracellular phosphorylation that is shown here to completely change the nature of PEDF from a neutrophic to an antiangiogenic factor. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Li, Z. Huang, R. Kingsley, X. Zhou, F. Li, D. W. Parke II, and W. Cao Biochemical Alterations in the Retinas of Very Low-Density Lipoprotein Receptor Knockout Mice: An Animal Model of Retinal Angiomatous Proliferation Arch Ophthalmol, June 1, 2007; 125(6): 795 - 803. [Abstract] [Full Text] [PDF] Z. Valnickova, S. V. Petersen, S. B. Nielsen, D. E. Otzen, and J. J. Enghild Heparin Binding Induces a Conformational Change in Pigment Epithelium-derived Factor J. Biol. Chem., March 2, 2007; 282(9): 6661 - 6667. [Abstract] [Full Text] [PDF] A. A. Kramerov, M. Saghizadeh, H. Pan, A. Kabosova, M. Montenarh, K. Ahmed, J. S. Penn, C. K. Chan, D. R. Hinton, M. B. Grant, et al. Expression of Protein Kinase CK2 in Astroglial Cells of Normal and Neovascularized Retina Am. J. Pathol., May 1, 2006; 168(5): 1722 - 1736. [Abstract] [Full Text] [PDF] G. Maik-Rachline and R. Seger Variable phosphorylation states of pigment-epithelium-derived factor differentially regulate its function Blood, April 1, 2006; 107(7): 2745 - 2752. [Abstract] [Full Text] [PDF]

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