Coupling of the IL2 receptor complex with non-receptor protein tyrosine kinases.

Abstract

IL2 induces the proliferation of T lymphocytes through the IL2 receptor (IL2R) following T lymphocyte activation. The IL2R consists of at least three subunits, IL2R alpha, beta and gamma chains. The cytoplasmic regions of the IL2R beta and gamma chains are critical for transduction of the IL2 signal to the cell interior. Although IL2R beta and gamma chains lack an intrinsic protein tyrosine kinase (PTK) domain, these chains recruit various non-receptor type PTKs, such as p56lck (and other Src family PTKs), Jak PTKs and Syk PTKs. The recruited PTKs are then activated following ligand stimulation to invoke intracellular signalling for the cell proliferation. Furthermore, it has been demonstrated that the IL2R is linked to at least three distinct signalling pathways leading to the induction of the c-fos/c-jun genes, c-myc gene induction and bcl-2 gene induction. All these pathways are essential for IL2 mediated proliferative signalling and co-operate with each other to ensure a full scale signal transduction. These signalling pathways, except that for bcl-2 pathway, appear to be mediated by multiple PTKs: p56lck is critical for the induction of the c-fos/c-jun genes, the activation of Syk PTKs results in the induction of the c-myc gene and Jak3 PTK is required for the induction of both c-fos and c-myc genes. Finally, the IL2 system may serve as a prototype in understanding the pleiotropic function of cytokine receptors that lack intrinsic PTK domains; the cytoplasmic structures of these cytokine receptors have evolved to allow the combined action of different PTK family members (and other signalling molecules) expressed in different cell types, which may determine the activity of cytokines.