Suppressor of cytokine signaling (SOCS) 2, a protein with multiple functions.
Cytokine receptors act through a complex signaling network, involving Janus kinases (JAKs) and the signal transducers and activators of transcription (STATs), to regulate diverse biological processes which control growth, development, homeostasis and immune function, among others. The JAK/STAT signaling pathway is attenuated via three mechanisms controlling the initiation, magnitude, and duration of the signal: the PIAS proteins, which prevent STAT dimerization or DNA interaction, the SHP phosphatases, which dephosphorylate activating tyrosine phosphorylations, and the suppressors of cytokine signaling (SOCS), which are transcribed in response to cytokine stimulation and use several interconnected mechanisms to downregulate the signal. Specific studies targeting the SOCS genes in vivo have unveiled SOCS2 as the main regulator of somatic growth through regulation of GH/IGF-1 signaling. In addition, several studies indicate that SOCS2 also has important actions in the central nervous system, the regulation of metabolism, the immune response, the mammary gland development, cancer, and other cytokine-dependent signaling pathways. Consistent with the role of cytokines in human physiology, any SOCS2 imbalance could result in a broad range of pathologies such as cardiovascular diseases, insulin resistance, cancer, and severe infections, among others. Thus, determining the importance of SOCS2 in health and disease will no doubt aid in the development of novel therapeutic strategies. In this review, we attempt to summarize the available information, including our results, regarding the role of SOCS2 in several biological processes.
Rico-Bautista
Elizabeth
E
Molecular Endocrinology Group, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
Flores-Morales
Amilcar
A
Fernández-Pérez
Leandro
L
D000818:Animals; D001846:Bone Development; D016207:Cytokines / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D009420:Nervous System / Q000254:growth & development; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D016207:Cytokines; C106643:SOCS2 protein, human; C491409:Socs2 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins