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J. Biol. Chem., Vol. 282, Issue 14, 10153-10163, April 6, 2007

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A Network-based Analysis of Polyanion-binding Proteins Utilizing Human Protein Arrays^*

Nazila Salamat-Miller, Jianwen Fang, Christopher W. Seidel^¶, Yassen Assenov^||, Mario Albrecht^||, and C. Russell Middaugh¹

From the Department of Pharmaceutical Chemistry and Bioinformatics Core Facility, University of Kansas, Lawrence, Kansas 66047, ^¶Stowers Institute for Medical Research, Kansas City, Missouri 64110, and ^||Max Planck Institute for Informatics, Stuhlsatzenhausweg 85, 66123 Saarbrücken, Germany

The existence of interactions between many cellular proteins and various polyanionic surfaces within a cell is now well established. The functional role of such interactions, however, remains to be clearly defined. The existence of protein arrays, with a large selection of different kinds of proteins, provides a way to better address a number of aspects of this question. We have therefore investigated the interaction between five cellular polyanions (actin, tubulin, heparin, heparan sulfate, and DNA) and 5,000 human proteins using protein microarrays in an attempt to better understand the functional nature of such interaction(s). We demonstrate that a large number of polyanion-binding proteins exist that contain multiple positively charged regions, are often disordered, are involved in phosphorylation processes, and appear to play a role in protein-protein interaction networks. Considering the crowded nature of cellular interiors, we propose that polyanion-binding proteins interact with a wide variety of polyanionic surfaces in cells in a functionally significant manner.

Received for publication, November 28, 2006 , and in revised form, January 31, 2007.

^* This work was supported in part by Kansas IDeA Network of Biomedical Research Excellence Bioinformatics Core and National Institutes of Health Grant P20 RR016475. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1–4, Tables 1–5, and additional references.

¹ To whom correspondence should be addressed: Dept. of Pharmaceutical Chemistry, University of Kansas, 2030 Becker Dr., Lawrence, KS 66047. Tel.: 875-864-5813; Fax: 875-864-5814; E-mail: middaugh{at}ku.edu.

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				J. Fang, Y. Dong, N. Salamat-Miller, and C. Russell Middaugh DB-PABP: a database of polyanion-binding proteins Nucleic Acids Res., January 11, 2008; 36(suppl_1): D303 - D306. [Abstract] [Full Text] [PDF]