ASSOCIATION OF P56(LCK) WITH IL-2 RECEPTOR BETA-CHAIN IS CRITICAL FOR THE IL-2-INDUCED ACTIVATION OF P56(LCK)

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-2Rbeta) 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-2Rbeta (either the wild-type or mutant forms) and mouse p56lck at high levels. BAF-B03 cells expressing a mutant IL-2Rbeta 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-2Rbeta 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-2Rbeta 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-2Rbeta 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.