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The Nck-Interacting Kinase Phosphorylates ERM Proteins for Formation of Lamellipodium by Growth Factors

Martin Baumgartner, Amy L. Sillman, Elizabeth M. Blackwood, Jyoti Srivastava, Nikki Madson, James W. Schilling, Jocelyn H. Wright and Diane L. Barber
Proceedings of the National Academy of Sciences of the United States of America
Vol. 103, No. 36 (Sep. 5, 2006), pp. 13391-13396
Stable URL: http://www.jstor.org/stable/30050797
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
The Nck-Interacting Kinase Phosphorylates ERM Proteins for Formation of Lamellipodium by Growth Factors
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Abstract

The mammalian Ste20-like Nck-interacting kinase (NIK) and its orthologs Misshapen in Drosophila and Mig-15 in Caenorhabditis elegans have a conserved function in regulating cell morphology, although through poorly understood mechanisms. We report two previously unrecognized actions of NIK: regulation of lamellipodium formation by growth factors and phosphorylation of the ERM proteins ezrin, radixin, and moesin. ERM proteins regulate cell morphology and plasma membrane dynamics by reversibly anchoring actin filaments to integral plasma membrane proteins. In vitro assays show that NIK interacts directly with ERM proteins, binding their N termini and phosphorylating a conserved C-terminal threonine. In cells, NIK and phosphorylated ERM proteins localize at the distal margins of lamellipodia, and NIK activity is necessary for phosphorylation of ERM proteins induced by EGF and PDGF, but not by thrombin. Lamellipodium extension in response to growth factors is inhibited in cells expressing a kinase-inactive NIK, suppressed for NIK expression with siRNA oligonucleotides, or expressing ezrin T567A that cannot be phosphorylated. These data suggest that direct phosphorylation of ERM proteins by NIK constitutes a signaling mechanism controlling growth factor-induced membrane protrusion and cell morphology.

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