SOCS negative regulation of the JAK-STAT pathway

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) canonical signal transduction pathway is activated primarily by cytokines, hormones, and growth factors and has been shown to play a role in many intracellular processes including cell differentiation, adaptive and innate immune responses, and cell growth. The JAK-STAT pathway has also been implicated to affect a wide variety of hematologic and non-hematologic diseases such as cancer and renal disease. JAK-STAT pathway activation is achieved through extracellular ligand binding resulting in transcription factor and receptor interactions and subsequent gene expression. Given the importance of the JAK-STAT pathway in human cellular functions, the regulation of this signal transduction pathway is vitally important. The current review focuses on the JAK-STAT pathway as well as the structure and function of the primary negative regulatory proteins of the JAK-STAT pathway, the suppressors of cytokine signaling (SOCS) proteins. SOCS proteins facilitate the negative regulation of signal transduction pathways by targeting specific signaling components for proteosomal destruction. Understanding the role of SOCS proteins in disease progression is of great importance to microbiologists and immunologists. Much research is directed at identifying and developing specific JAK-STAT inhibitors and SOCS inhibitors that may prove useful in counteracting the cellular effects observed in many carcinomas and infectious diseases.