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 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 Buss, J E Articles by Sefton, B M Search for Related Content PubMed PubMed Citation Articles by Buss, J E Articles by Sefton, B M

 Previous Article  |  Next Article 

J Virol. 1986 May; 58(2): 468-474

The absence of myristic acid decreases membrane binding of p60src but does not affect tyrosine protein kinase activity.

ABSTRACT

We have constructed two point mutants of Rous sarcoma virus in which the amino-terminal glycine residue of the transforming protein, p60src, was changed to an alanine or a glutamic acid residue. Both mutant proteins failed to become myristylated and, more importantly, no longer transformed cells. The lack of transformation could not be attributed to defects in the catalytic activity of the mutant p60src proteins. In vitro phosphorylation of the peptide angiotensin or of the cellular substrate proteins enolase and p36 revealed no significant differences in the Km or specific activity of the mutant and wild-type p60src proteins. However, when cellular fractions were prepared, less than 12% of the nonmyristylated p60src proteins was bound to membranes. In contrast, more than 82% of the wild-type protein was associated with membranes. Wild-type p60src was phosphorylated by protein kinase C, a protein kinase which associates with membranes when activated. The mutant proteins were not. This finding supports the idea that within the intact cell the nonmyristylated p60src proteins are cytoplasmic and suggests that this apparent solubility is not an artifact of the cell fractionation procedure. The myristyl groups of p60src apparently encourages a tight association between protein and membranes and, by determining the cellular location of the enzyme, allows transformation to occur.

This article has been cited by other articles:

• Zaman, S. N., Resek, M. E., Robbins, S. M. (2008). Dual acylation and lipid raft association of Src-family protein tyrosine kinases are required for SDF-1/CXCL12-mediated chemotaxis in the Jurkat human T cell lymphoma cell line. J. Leukoc. Biol. 84: 1082-1091 [Abstract] [Full Text]  
• Shvartsman, D. E., Donaldson, J. C., Diaz, B., Gutman, O., Martin, G. S., Henis, Y. I. (2007). Src kinase activity and SH2 domain regulate the dynamics of Src association with lipid and protein targets. J. Cell Biol. 178: 675-686 [Abstract] [Full Text]  
• Ducker, C. E., Upson, J. J., French, K. J., Smith, C. D. (2005). Two N-Myristoyltransferase Isozymes Play Unique Roles in Protein Myristoylation, Proliferation, and Apoptosis. Mol Cancer Res 3: 463-476 [Abstract] [Full Text]  
• Sotgia, F., Razani, B., Bonuccelli, G., Schubert, W., Battista, M., Lee, H., Capozza, F., Schubert, A. L., Minetti, C., Buckley, J. T., Lisanti, M. P. (2002). Intracellular Retention of Glycosylphosphatidyl Inositol-Linked Proteins in Caveolin-Deficient Cells. Mol. Cell. Biol. 22: 3905-3926 [Abstract] [Full Text]  
• Jin, F, Reynolds, A., Hines, M., Jensen, P., Johnson, K., Wheelock, M. (1999). Src induces morphological changes in A431 cells that resemble epidermal differentiation through an SH3- and Ras-independent pathway. J. Cell Sci. 112: 2913-2924 [Abstract]  
• Saouaf, S. J., Kut, S. A., Fargnoli, J., Rowley, R. B., Bolen, J. B., Mahajan, S. (1995). Reconstitution of the B Cell Antigen Receptor Signaling Components in COS Cells. J. Biol. Chem. 270: 27072-27078 [Abstract] [Full Text]  
• Martin, G., Brommonschenkel, S., Chunwongse, J, Frary, A, Ganal, M., Spivey, R, Wu, T, Earle, E., Tanksley, S. (1993). Map-based cloning of a protein kinase gene conferring disease resistance in tomato. Science 262: 1432-1436 [Abstract]  
• Spencer, D., Wandless, T., Schreiber, S., Crabtree, G. (1993). Controlling signal transduction with synthetic ligands. Science 262: 1019-1024 [Abstract]  
• David-Pfeuty, T, Bagrodia, S, Shalloway, D (1993). Differential localization patterns of myristoylated and nonmyristoylated c-Src proteins in interphase and mitotic c-Src overexpresser cells. J. Cell Sci. 105: 613-628 [Abstract]  
• Graff, J., Gordon, J., Blackshear, P. (1989). Myristoylated and nonmyristoylated forms of a protein are phosphorylated by protein kinase C. Science 246: 503-506 [Abstract]  
• Buss, J., Solski, P., Schaeffer, J., MacDonald, M., Der, C. (1989). Activation of the cellular proto-oncogene product p21Ras by addition of a myristylation signal. Science 243: 1600-1603 [Abstract]  
• Duronio, R., Towler, D., Heuckeroth, R., Gordon, J. (1989). Disruption of the yeast N-myristoyl transferase gene causes recessive lethality. Science 243: 796-800 [Abstract]  
• Wilcox, C, Hu, J., Olson, E. (1987). Acylation of proteins with myristic acid occurs cotranslationally. Science 238: 1275-1278 [Abstract]  
• Burn, P, Burger, M. (1987). The cytoskeletal protein vinculin contains transformation-sensitive, covalently bound lipid. Science 235: 476-479 [Abstract]