The protein tyrosine kinase p56lck regulates thymocyte development independently of its interaction with CD4 and CD8 coreceptors [corrected].
The lck gene encodes a lymphocyte-specific protein tyrosine kinase of the nonreceptor type that is implicated in signal transduction pathways emanating from the CD4 and CD8 coreceptors. Previous studies also support a role for p56lck in regulating T cell receptor beta gene rearrangements and, more generally, thymocyte development. Here we report that a mutant form of p56lck, which is incapable of interacting with CD4 or CD8, behaves indistinguishably from association-competent p56lck with respect to its ability to affect thymocyte maturation. The effects of p56lck remained specific in that the closely related src-family kinase p59hck was incapable of substituting for p56lck in arresting beta locus gene rearrangements. These data support the view that src-family kinases perform highly specialized and often nonoverlapping functions in hematopoietic cells, and that p56lck acts independently of its association with CD4 and CD8 to regulate thymocyte development.
Levin
S D
SD
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
Abraham
K M
KM
Anderson
S J
SJ
Forbush
K A
KA
Perlmutter
R M
RM
D000818:Animals; D015704:CD4 Antigens / Q000502:physiology*; D016827:CD8 Antigens / Q000502:physiology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D011518:Proto-Oncogene Proteins; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)