Association of p56lck with IL-2 receptor beta chain is critical for the IL-2-induced activation of p56lck.
Previous studies demonstrate that p56lck, a member of the src-family of protein tyrosine kinases (PTKs), can physically associate with the interleukin-2 (IL-2) receptor beta chain (IL-2R beta) and that IL-2 receptor engagement stimulates p56lck activity. To examine the mechanisms underlying p56lck PTK activation by IL-2, we established a mouse pro-B cell line, BAF-B03, expressing both IL-2R beta (either the wild-type or mutant forms) and mouse p56lck at high levels. BAF-B03 cells expressing a mutant IL-2R beta chain lacking an 'acidic' region of the cytoplasmic domain, previously shown to be essential for association with p56lck, fail to induce p56lck PTK activation upon IL-2 stimulation. This suggests that the association of p56lck with the IL-2R beta chain, despite its low stoichiometry, is required for the activation of cellular p56lck PTK upon IL-2 stimulation. Intriguingly, BAF-B03 cells expressing an IL-2R beta chain which lacks a different cytoplasmic region, the 'serine-rich' region, also fail to activate p56lck in response to IL-2. Hence, physical association of p56lck with the IL-2R beta chain is not by itself sufficient to permit IL-2-mediated regulation of this PTK. Additional experiments suggest that one result of PTK activation is the accumulation of c-fos and c-jun transcripts.
Minami
Y
Y
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Kono
T
T
Yamada
K
K
Kobayashi
N
N
Kawahara
A
A
Perlmutter
R M
RM
Taniguchi
T
T
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology; D002478:Cells, Cultured; D004789:Enzyme Activation; D015870:Gene Expression; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)