IL-5 RECEPTOR-MEDIATED TYROSINE PHOSPHORYLATION OF SH2 SHS-CONTAININGPROTEINS AND ACTIVATION OF BRUTON TYROSINE AND JANUS-2 KINASES/

Interleukin 5 (IL-5) induces proliferation and differentiation of B ce lls and eosinophils by interacting with its receptor (IL-5R) which con sists of two distinct polypeptide chains, alpha and beta (pc). Althoug h both IL-5R alpha and beta c lack a kinase catalytic domain, IL-5 is capable of inducing tyrosine phosphorylation of cellular proteins. We investigated the role of IL-5R alpha in tyrosine phosphorylation of mo lecules involved in IL-5 signal transduction, using an IL-5-dependent early B cell line, Y16 and transfectants expressing intact or mutant I L-5R alpha together with intact beta c. The results revealed that the transfectants expressing truncated IL-5R alpha, which entirely lacks a cytoplasmic domain, together with beta c, showed neither protein-tyro sine phosphorylation nor proliferation in response to IL-5. This confi rms that IL-5R alpha plays a critical role in protein-tyrosine phospho rylation which triggers cell growth. IL-5 stimulation results in rapid tyrosine phosphorylation of pc and proteins containing Src homology 2 (SH2) and/or SH3 domains such as phosphatidyl-inosito1-3 kinase, Shc, Vav, and HS1, suggesting their involvement in IL-5-mediated signal tr ansduction. IL-5 stimulation significantly enhanced activities of Janu s 2 and B cell-specific Bruton's tyrosine kinases (JAK2 and Btk) and i ncreased the tyrosine phosphorylation of JAK2 kinase. These results an d recent data on signaling of growth factors taken together, multiple biochemical pathways driven by tyrosine kinases such as JAK2 and Btk a re involved in IL-5 signal transduction.