This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhou, F. Articles by Geahlen, R. L. Search for Related Content PubMed PubMed Citation Articles by Zhou, F. Articles by Geahlen, R. L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2006, p. 3478-3491, Vol. 26, No. 9
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.9.3478-3491.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Nucleocytoplasmic Trafficking of the Syk Protein Tyrosine Kinase

Fei Zhou, Jianjie Hu, Haiyan Ma, Marietta L. Harrison, and Robert L. Geahlen^*

Department of Medicinal Chemistry and Molecular Pharmacology and Purdue Cancer Center, Purdue University, West Lafayette, Indiana 47907

Received 29 December 2005/ Returned for modification 25 January 2006/ Accepted 7 February 2006

The protein tyrosine kinase Syk couples the B-cell receptor (BCR) for antigen to multiple intracellular signaling pathways and also modulates cellular responses to inducers of oxidative stress in a receptor-independent fashion. In B cells, Syk is found in both the nuclear and cytoplasmic compartments but contains no recognizable nuclear localization or export signals. Through the analysis of a series of deletion mutants, we identified the presence of an unconventional shuttling sequence near the junction of the catalytic domain and the linker B region that accounts for Syk's subcellular localization. This localization is altered following prolonged engagement of the BCR, which causes Syk to be excluded from the nucleus. Nuclear exclusion requires the receptor-mediated activation of protein kinase C and new protein synthesis. Both of these processes also potentiate the activation of caspase 3 in cells in response to oxidative stress in a manner that is dependent on the localization of Syk outside of the nucleus. In contrast, restriction of Syk to the nucleus greatly diminishes the stress-induced activation of caspase 3.

F.Z. and J.H. have equal first authorship.

Present address: BioNumerik Pharmaceuticals, Inc., San Antonio, TX 78229.

This article has been cited by other articles:

• Zhang, Y., Oh, H., Burton, R. A., Burgner, J. W., Geahlen, R. L., Post, C. B. (2008). Tyr130 phosphorylation triggers Syk release from antigen receptor by long-distance conformational uncoupling. Proc. Natl. Acad. Sci. USA 105: 11760-11765 [Abstract] [Full Text]  
• Lau, C., Wang, X., Song, L., North, M., Wiehler, S., Proud, D., Chow, C.-W. (2008). Syk Associates with Clathrin and Mediates Phosphatidylinositol 3-Kinase Activation during Human Rhinovirus Internalization. J. Immunol. 180: 870-880 [Abstract] [Full Text]  
• Luangdilok, S., Box, C., Patterson, L., Court, W., Harrington, K., Pitkin, L., Rhys-Evans, P., O-charoenrat, P., Eccles, S. (2007). Syk Tyrosine Kinase Is Linked to Cell Motility and Progression in Squamous Cell Carcinomas of the Head and Neck. Cancer Res. 67: 7907-7916 [Abstract] [Full Text]