Interaction of the IL-2 receptor with the src-family kinase p56lck: identification of novel intermolecular association.
In the interleukin-2 (IL-2) system, intracellular signal transduction is triggered by the beta chain of the IL-2 receptor (IL-2R beta); however, the responsible signaling mechanism remains unidentified. Evidence for the formation of a stable complex of IL-2R beta and the lymphocyte-specific protein tyrosine kinase p56lck is presented. Specific association sites were identified in the tyrosine kinase catalytic domain of p56lck and in the cytoplasmic domain of IL-2R beta. As a result of interaction, IL-2R beta became phosphorylated in vitro by p56lck. Treatment of T lymphocytes with IL-2 promotes p56lck kinase activity. These data suggest the participation of p56lck as a critical signaling molecule downstream of IL-2R via a novel interaction.
Hatakeyama
M
M
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Kono
T
T
Kobayashi
N
N
Kawahara
A
A
Levin
S D
SD
Perlmutter
R M
RM
Taniguchi
T
T
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001483:Base Sequence; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D015345:Oligonucleotide Probes; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
D015703:Antigens, CD; D007376:Interleukin-2; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)