Cbp deficiency alters Csk localization in lipid rafts but does not affect T-cell development.
The ubiquitously expressed transmembrane adaptor Csk-binding protein (Cbp) recruits Csk to lipid rafts, where the latter exerts its negative regulatory effect on the Src family of protein tyrosine kinases. We have inactivated Cbp in the mouse germ line. In contrast to Csk gene inactivation, which leads to embryonic lethality and impaired T-cell development, Cbp-deficient mice were viable and exhibited normal T-cell development but with an increased thymocyte population. In the absence of Cbp, the amount of Csk that localizes to the lipid rafts was greatly reduced. Interestingly, this altered lipid raft localization of Csk did not lead to any detectable biochemical or functional defect in T cells. The T-cell receptor-induced intracellular calcium flux, cell proliferation, and cytokine secretion were not affected by the absence of Cbp. Peripheral T-cell tolerance to superantigen SEB was also largely intact in Cbp-deficient mice. Thus, Cbp is dispensable for T-cell development and activation.
Xu
Shengli
S
Laboratory of Immunology, Center for Molecular Medicine, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Lab 6-15, Proteos, Singapore 138673, Singapore.
Huo
Jianxin
J
Tan
Joy En-Lin
JE
Lam
Kong-Peng
KP
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D000081247:CSK Tyrosine-Protein Kinase; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004720:Endonucleases / Q000378:metabolism; D004768:Enterotoxins / Q000378:metabolism; D005434:Flow Cytometry; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000097:blood / Q000737:chemistry; D008198:Lymph Nodes / Q000378:metabolism; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008957:Models, Genetic; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D010770:Phosphotransferases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D019061:src-Family Kinases
D001323:Autoantibodies; D015704:CD4 Antigens; D016827:CD8 Antigens; D018076:DNA, Complementary; D004768:Enterotoxins; D007074:Immunoglobulin G; D008565:Membrane Proteins; C498709:Pag1 protein, mouse; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C031818:enterotoxin B, staphylococcal; D010770:Phosphotransferases; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D004720:Endonucleases; D002118:Calcium