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Molecular and Cellular Biology, June 2000, p. 3906-3917, Vol. 20, No. 11
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Interaction between PAK and Nck: a Template for Nck Targets and Role of PAK Autophosphorylation

Zhou-shen Zhao,1 Edward Manser,1,* and Louis Lim1,2

Glaxo-IMCB Group, Institute of Molecular & Cell Biology, Singapore 117609, Singapore,1 and Department of Neurochemistry, Institute of Neurology, University College London, London WC1N 1PJ, United Kingdom2

Received 4 October 1999/Returned for modification 1 December 1999/Accepted 5 March 2000

The kinase PAK binds tightly to the SH3 domain of its partner PIX via a central proline-rich sequence. A different N-terminal sequence allows alpha PAK to bind an SH3 domain of the adaptor Nck. The Nck SH3[2] domain interacts equally with an 18-mer PAK-derived peptide and full-length alpha PAK. Detailed analysis of this binding by saturation substitution allows related Nck targets to be accurately identified from sequence characteristics alone. All Nck SH3[2] binding proteins, including PAK, NIK, synaptojanin, PRK2, and WIP, possess the motif PXXPXRXXS; in the case of PAK, serine phosphorylation at this site negatively regulates binding. We show that kinase autophosphorylation blocks binding by both Nck and PIX to alpha PAK, thus providing a mechanism to regulate PAK interactions with its SH3-containing partners. One cellular consequence of the regulatable binding of PAK is facilitation of its cycling between cytosolic and focal complex sites.

* Corresponding author. Mailing address: Glaxo-IMCB Group, Institute of Molecular & Cell Biology, 30 Medical Dr., Singapore 117609, Singapore. Phone: (65) 874-6167. Fax: (65) 774-0742. E-mail: mcbmansr{at}imcb.nus.edu.sg.

Molecular and Cellular Biology, June 2000, p. 3906-3917, Vol. 20, No. 11
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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