This Article 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 Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wright, D D Articles by Kamps, M P Search for Related Content PubMed PubMed Citation Articles by Wright, D D Articles by Kamps, M P

Oncogenic activation of the Lck protein accompanies translocation of the LCK gene in the human HSB2 T-cell leukemia.

Department of Pathology, University of California, School of Medicine, San Diego, La Jolla 92093-0612.

ABSTRACT

The tyrosine protein kinase p56lck transduces signals important for antigen-induced T-cell activation. In transgenic mice, p56lck is oncogenic when overexpressed or expressed as a mutant, catalytically activated enzyme. In humans, the LCK gene is located at the breakpoint of the t(1;7)(p34;q34) chromosomal translocation. This translocation positions the beta T-cell receptor constant region enhancer upstream of the LCK gene without interrupting the LCK coding sequences, and a translocation of this sort occurs in both the HSB2 and the SUP-T-12 T-cell lines. We have found that, although the level of the p56lck protein in HSB2 cells is elevated approximately 2-fold in comparison with that in normal T-cell lines, total cellular tyrosine protein phosphorylation is elevated approximately 10-fold. Increased levels of phosphotyrosine in HSB2 cells resulted from mutations in the LCK gene that activated its function as a phosphotransferase and converted it into a dominant transforming oncogene. The oncogenic p56lck in HSB2 cells contained one amino acid substitution within the CD4/CD8-binding domain, two substitutions in the kinase domain, and an insertion of Gln-Lys-Pro (QKP) between the SH2 and kinase domains. In NIH 3T3 fibroblasts, three of these mutations cooperated to produce the fully oncogenic form of this p56lck variant. These results suggest that mutation of LCK may contribute to some human T-cell leukemias.

This article has been cited by other articles:

• Miertzschke, M., Stanley, P., Bunney, T. D., Rodrigues-Lima, F., Hogg, N., Katan, M. (2007). Characterization of Interactions of Adapter Protein RAPL/Nore1B with RAP GTPases and Their Role in T Cell Migration. J. Biol. Chem. 282: 30629-30642 [Abstract] [Full Text]  
• Shi, M., Cooper, J. C., Yu, C.-L. (2006). A Constitutively Active Lck Kinase Promotes Cell Proliferation and Resistance to Apoptosis through Signal Transducer and Activator of Transcription 5b Activation. Mol Cancer Res 4: 39-45 [Abstract] [Full Text]  
• Bénistant, C., Bourgaux, J.-F., Chapuis, H., Mottet, N., Roche, S., Bali, J.-P. (2001). The COOH-Terminal Src Kinase Csk Is a Tumor Antigen in Human Carcinoma. Cancer Res. 61: 1415-1420 [Abstract] [Full Text]  
• Abe, K., Whitehead, I. P., O'Bryan, J. P., Der, C. J. (1999). Involvement of NH2-terminal Sequences in the Negative Regulation of Vav Signaling and Transforming Activity. J. Biol. Chem. 274: 30410-30418 [Abstract] [Full Text]  
• Hartley, D. A., Hurley, T. R., Hardwick, J. S., Lund, T. C., Medveczky, P. G., Sefton, B. M. (1999). Activation of the Lck Tyrosine-protein Kinase by the Binding of the Tip Protein of Herpesvirus Saimiri in the Absence of Regulatory Tyrosine Phosphorylation. J. Biol. Chem. 274: 20056-20059 [Abstract] [Full Text]  
• Fukazawa, T., Reedquist, K. A., Trub, T., Soltoff, S., Panchamoorthy, G., Druker, B., Cantley, L., Shoelson, S. E., Band, H. (1995). The SH3 Domain-binding T Cell Tyrosyl Phosphoprotein p120. J. Biol. Chem. 270: 19141-19150 [Abstract] [Full Text]