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Abstract
Lymphocyte populations in the immune system are maintained by a well-organized balance between cellular proliferation, cellular survival and programmed cell death (apoptosis(. One of the primary functions of many cytokines is to coordinate these processes. In particular, the interleukin (IL(‐2 family of cytokines, which consists of six cytokines ‐IL‐2, IL‐4, IL‐7, IL‐9, IL‐15 and IL‐21) that all share a common receptor subunit (gc), plays a major role in promoting and maintaining T lymphocyte populations. The details of the molecular signaling pathways mediated by these cytokines have not been fully elucidated. However, the three major pathways clearly involved include the JAK/STAT, MAPK and phosphatidylinositol 3‐kinase ‐PI3K‐ pathways. The details of these pathways as they apply to the IL‐2 family of cytokines is discussed, with a focus on their roles in proliferation and survival signaling.
| Abbreviations | ||
| IL‐: | = | Interleukin |
| PI3K: | = | phosphatidylinositol‐3 kinase |
| γc: | = | common γ |
| XSCID: | = | X‐linked severe combined immunodeficiency |
| MAPK: | = | mitogen activated protein kinase |
| PTK: | = | protein tyrosine kinase |
| STAT: | = | signal transducer and activator of transcription |
| SOS: | = | Son of Sevenles |
| = | mitogen activated protein kinase | |
| p90Rsk: | = | 90 kDa ribosomal S6 kinases |
| ATF: | = | activating transcription factor |
| SAPK: | = | stress‐activated protein kinase |
| JNK: | = | Jun‐N‐terminal kinase |
| LPS: | = | lipopolysaccharide |
| FRIP: | = | IL‐4 interacting protein |
| RasGAP: | = | Ras GTPase activating protein |
| SH2: | = | SRC‐homology domain 2 |
| IRS: | = | insulin receptor substrate |
| GAB: | = | Grb2‐associated binding protein |
| NK: | = | natural killer |
| PTB: | = | phosphotyrosine binding |
| PDK1: | = | phosphoinositide‐dependent protein kinase 1 |
| FOXO: | = | Forkhead box, class O |
| IAP: | = | inhibitor of apoptosis protein |
| GSK‐3: | = | glycogen synthase kinase‐3 |
| p70S6K: | = | 40S ribosomal protein S6 kinase |
| SHIP: | = | SH2‐domain containing inositol polyphosphatases |
| PTEN: | = | phosphatase and tensin homologue deleted on chromosome 10 |
| TCR: | = | T cell antigen receptor |
| BCR: | = | B cell antigen receptor |
| PH: | = | pleckstrin homology |
| GM‐CSF: | = | granulocyte‐macrophage colony stimulating factor |
| cdk: | = | cyclin‐dependent kinase |
| CDKI: | = | cyclin‐dependent kinase inhibitors |
| Rb: | = | retinoblastoma tumor suppressor protein |