The interleukin-2 receptor complex and signal transduction: role of the beta-chain.
Proliferation of lymphocytes is regulated by a variety of cytokines, among which interleukin-2 (IL-2) is well characterized for its potent ability to promote cell growth. The IL-2 signal(s) is transmitted to the cell interior via its homologous receptor (IL-2R). The functional high affinity IL-2R is a multichain complex consisting of at least three distinct components, IL-2R alpha, beta and gamma. None of these components possess an intrinsic protein tyrosine kinase (PTK) domain. cDNA expression studies, have revealed the critical role of IL-2R beta, but not IL-2R alpha, in the IL-2R-mediated intracellular signaling process. Studies utilizing mutants of IL-2R beta identified an essential cytoplasmic region, defined as the 'serine-rich' region, for IL-2-induced cell growth. With respect to the involvement of PTK(s) in IL-2R mediated signal transduction, it has been demonstrated that p56lck, a member of the src-family PTKs interacts with the IL-2R beta. In fact, IL-2 stimulation increases the PTK activity of p56lck. Another cytoplasmic region of the receptor, defined as the 'acidic' region has been found to be critical for the association of p56lck with the IL-2R beta. Interestingly the 'serine-rich' and 'acidic' regions of IL-2R beta are both required for the PTK activation of p56lck. Expression studies with mutant IL-2R beta cDNAs have revealed a bifurcation in the IL-2 signaling pathway. One pathway involves the src-family PTK activation which is linked to the activation of p21ras and the subsequent induction of c-fos/c-jun protooncogenes.(ABSTRACT TRUNCATED AT 250 WORDS)
Kono
T
T
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Minami
Y
Y
Taniguchi
T
T
D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D011518:Proto-Oncogene Proteins / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D015375:Receptors, Interleukin-2; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)