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Regulation and function of the Lck proto-oncogene product

lck is a member of the src family of tyrosine protein kinase genes expressed predominantly in T-lymphocytes. Its product, p56$ sp{ rm lck}$ is physically and functionally associated with the CD4 and CD8 T-cell surface antigens, suggesting a possible role in CD4/CD8-mediated tyrosine phosphorylation signals during the process of antigen stimulation. Activation of p56$ sp{ rm lck}$ by mutation of tyrosine 505 was prevented by further mutation of either the site of autophosphorylation, tyrosine 394 to phenylalanine, or the site of myristylation, glycine 2 to alanine, as determined by the effects of overexpression of these p56$ sp{ rm lck}$ mutants in rodent fibroblasts. The role of activation of p56$ sp{ rm lck}$ in T-cells was examined by overexpression of the tyrosine 505-to-phenylalanine mutant in a CD4-negative, MHC-class II restricted T-cell hybridoma. The enhancement of T-cell responsiveness observed with expression of activated Lck was qualitatively similar to the effect of expression of CD4 in these cells, providing evidence that p56$ sp{ rm lck}$ positively regulates T-cell functions and that it mediates some of the functions of CD4 and CD8 during antigen stimulation.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.60504
Date January 1991
CreatorsAbraham, Ninan
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Division of Experimental Medicine.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 001243463, proquestno: AAIMM72068, Theses scanned by UMI/ProQuest.

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