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 important for the growth and differentiation of T and B lymphocytes, natural killer cells, macrophages, and monocytes. These cytokines have overlapping biological effects that in part result from the use of the shared receptor subunit gamma c. Recently it has become clear that these cytokines activate a number of important intracellular signaling molecules, including the Janus kinases JAK1 and JAK3 and members of the transcription factor family of signal transducers and activators of transcription (STATs). The discovery of these signaling pathways has led to important new insights into their role in lymphocyte maturation, as it has emerged that mutations in the genes encoding both gamma c and JAK3 result in similar forms of severe combined immunodeficiency (SCID). In this review we examine the structure and function of cytokine receptors 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.
Johnston
J A
JA
The Lymphocyte Cell Biology Section, National Institute of Arthritis, Musculoskeletal and Skin Disease, National Institutes of Health, Bethesda, Maryland, USA.
Bacon
C M
CM
Riedy
M C
MC
O'Shea
J J
JJ
D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000502:physiology*; D004792:Enzyme Precursors / Q000502:physiology; D005796:Genes; D006801:Humans; D018664:Interleukin-12 / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D053616:Janus Kinase 3; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008214:Lymphocytes / Q000502:physiology; D019000:Phosphotyrosine / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D018121:Receptors, Cytokine / Q000502:physiology*; D050794:STAT1 Transcription Factor; D016511:Severe Combined Immunodeficiency / Q000503:physiopathology; D015398:Signal Transduction; D000072377:Syk Kinase; D015534:Trans-Activators / Q000502:physiology*; D018909:src Homology Domains; D019061:src-Family Kinases / Q000502:physiology
D004268:DNA-Binding Proteins; D004792:Enzyme Precursors; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D018121:Receptors, Cytokine; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D018664:Interleukin-12; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C000606896:SYK protein, human; D000072377:Syk Kinase; D019061:src-Family Kinases