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PNAS 104 (20): 8328-8333

Copyright © 2007 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / CELL BIOLOGY

Profiling signaling polarity in chemotactic cells

Yingchun Wang{dagger}, Shi-Jian Ding{ddagger}, Wei Wang{dagger}, Jon M. Jacobs{ddagger}, Wei-Jun Qian{ddagger}, Ronald J. Moore{ddagger}, Feng Yang{ddagger}, David G. Camp, II{ddagger}, Richard D. Smith{ddagger}, and Richard L. Klemke{dagger},§

{dagger}Department of Pathology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093; and {ddagger}Biological Sciences Division, Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99354

Edited by Peter N. Devreotes, Johns Hopkins University School of Medicine, Baltimore, MD, and approved April 10, 2007

Received for publication February 6, 2007.

Abstract: Cell movement requires morphological polarization characterized by formation of a leading pseudopodium (PD) at the front and a trailing rear at the back. However, little is known about how protein networks are spatially integrated to regulate this process at the system level. Here, we apply global proteome profiling in combination with newly developed quantitative phosphoproteomics approaches for comparative analysis of the cell body (CB) and PD proteome of chemotactic cells. The spatial relationship of 3,509 proteins and 228 distinct sites of phosphorylation were mapped revealing networks of signaling proteins that partition to the PD and/or the CB compartments. The major network represented in the PD includes integrin signaling, actin regulatory, and axon guidance proteins, whereas the CB consists of DNA/RNA metabolism, cell cycle regulation, and structural maintenance. Our findings provide insight into the spatial organization of signaling networks that control cell movement and provide a comprehensive system-wide profile of proteins and phosphorylation sites that control cell polarization.

Key Words: bioinformatics • chemotaxis • phosphoproteomics • proteomics • cell migration


Author contributions: Y.W. and S.-J.D. contributed equally to this work; Y.W., S.-J.D., W.W., and R.L.K. designed research; Y.W., S.-J.D., and W.W. performed research; Y.W., S.-J.D., F.Y., D.G.C., R.D.S., and R.L.K. contributed new reagents/analytic tools; Y.W., S.-J.D., J.M.J., W.-J.Q., R.J.M., and R.L.K. analyzed data; and Y.W., S.-J.D., J.M.J., R.D.S., and R.L.K. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/cgi/content/full/0701103104/DC1.

§To whom correspondence should be addressed. E-mail: rklemke{at}ucsd.edu

© 2007 by The National Academy of Sciences of the USA


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