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Serine 6 of Lck tyrosine kinase: a critical site for Lck myristoylation, membrane localization, and function in T lymphocytes.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2000 Sep 15; Vol. 165 (6), pp. 3226-31. - Publication Year :
- 2000
-
Abstract
- Lck is a member of the Src family kinases expressed predominantly in T cells, and plays a pivotal role in TCR-mediated signal transduction. Myristoylation of glysine 2 in the N-terminal Src homology 4 (SH4) domain of Lck is essential for membrane localization and function. In this study, we examined a site within the SH4 domain of Lck regulating myristoylation, membrane localization, and function of Lck. A Lck mutant in which serine 6 (Ser6) was substituted by an alanine was almost completely cytosolic in COS-7 cells, and this change of localization was associated with a drastic inhibition of myristoylation in this mutant. To assess the role of Ser6 of Lck in T cell function, we established stable transfectants expressing various Lck mutants using Lck-negative JCaM1 cells. The Lck mutant of Ser6 to alanine, most of which did not target to the plasma membrane, was not able to reconstitute TCR-mediated signaling events in JCaM1 cells, as analyzed by tyrosine phosphorylation of intracellular proteins and CD69 expression. These results demonstrate that Ser6 is a critical factor for Lck myristoylation, membrane localization, and function in T cells, presumably because the residue is important for N-myristoyl transferase recognition.
- Subjects :
- Alanine genetics
Amino Acid Substitution genetics
Amino Acid Substitution immunology
Animals
COS Cells
Cell Membrane enzymology
Cell Membrane genetics
Chlorocebus aethiops
Humans
Jurkat Cells
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) genetics
Membrane Proteins genetics
Mice
Mutagenesis, Site-Directed
Phosphorylation
Receptors, Antigen, T-Cell genetics
Receptors, Antigen, T-Cell metabolism
Serine genetics
T-Lymphocytes metabolism
Transfection
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) metabolism
Membrane Proteins metabolism
Myristic Acid metabolism
Serine metabolism
T-Lymphocytes enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 165
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 10975838
- Full Text :
- https://doi.org/10.4049/jimmunol.165.6.3226