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.
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
S D
SD
Levin
K M
KM
Abraham
S J
SJ
Anderson
K A
KA
Forbush
R M
RM
Perlmutter
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)