Premium
Critical role of the membrane‐proximal, proline‐rich motif of the interleukin‐2 receptor γc chain in the Jak3‐independent signal transduction
Author(s) -
Tsujino Shiho,
Miyazaki Tadaaki,
Kawahara Atsuo,
Maeda Michiyuki,
Taniguchi Tadatsugu,
Fujii Hodaka
Publication year - 1999
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.1999.00266.x
Subject(s) - biology , tyrosine , tyrosine phosphorylation , signal transduction , microbiology and biotechnology , phosphorylation , amino acid , mutant , biochemistry , gene
Background The interleukin‐2 receptor (IL‐2R) consists of three subunits, the IL‐2Rα, IL‐2Rβc, and IL‐2Rγc chains. The essential role of the IL‐2Rγc cytoplasmic domain, consisting of 86 amino acids, in signal transmission has been well documented. Particularly, the carboxyl ter‐minal region containing 48 amino acids. is essential for the association with and activation of the Jak3 protein tyrosine kinase. On the other hand, little is known about the role of the rest of the IL‐2Rγc cytoplasmic region consisting of the membrane‐proximal 38 amino acids. Results We show that a truncated mutant form of IL‐2Rγc which lacks the membrane‐distal 48 amino acids is still capable of inducing the activation of Jak1 and Stat3/Stat5 in the absence of Jak3 activation. This membrane‐proximal region can also mediate the IL‐2‐induced tyrosine phosphorylation of the p85 subunit of phosphatidylinositol‐3‐kinase (PI3K). Furthermore, these signalling events are completely abrogated when mutations are introduced into the proline‐rich motif in this region. Conclusions In this study, we identified a Jak3‐independent signalling pathway(s) from the membrane‐proximal region of IL‐2Rγc. Our results indicate that the proline‐rich motif in this region plays a critical role in this signalling pathway(s). The present study may provide further insight into the mechanism of cellular responses mediated by IL‐2 and other cytokines which utilize the IL‐2Rγc for their signal transmission.