SIGNALING BY IL-2 AND RELATED CYTOKINES - JAKS, STATS, AND RELATIONSHIP TO IMMUNODEFICIENCY

Cytokines that bind to the interleukin-2 (IL-2) receptor common gamma chain (gamma c), including IL-2, IL-4, IL-7, IL-9, and IL-15, are impo rtant for the growth and differentiation of T and B lymphocytes, natur al killer cells, macrophages, and monoctyes. These cytokines have over lapping biological effects that in part result from the use of the sha red receptor subunit gamma c. Recently it has become clear that these cytokines activate a number of important intracellular signaling molec ules, including the Janus kinases JAK1 and JAK3 and members of the tra nscription factor family of signal transducers and activators of trans cription (STATs). The discovery of these signaling pathways has led to important new insights into their role in lymphocyte maturation, as i t has emerged that mutations in the genes encoding both gamma c and JA K3 result in similar forms of severe combined immunodeficiency (SCID), In this review we examine the structure and function of cytokine rece ptors and the signaling pathways involved in their regulation of gene expression. Furthermore, we discuss recent advances that have led to a better understanding of how cytokines elicit intracellular responses, as well as their role in normal lymphoid development.