Intracellular Proteins and Mechanisms Involved in the Control of gp130/JAK/STAT Cytokine Signaling

• Autores: Carbia-Nagashima, A.; Arzt, E.
• Año de publicación: 2004
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: IUBMB Life 2004;56(2):83-88
• Materia: Cytokine; gp130; JAK; PIAS; SOCS; STAT; cell protein; cytokine; cytokine receptor; glycoprotein gp 130; interleukin 6; Janus kinase; proteasome; protein inhibitor of activated STAT; STAT protein; SUMO 1 protein; suppressor of cytokine signaling; ubiquitin; unclassified drug; animal cell; cell differentiation; cell proliferation; cell survival; cell transformation; embryo development; heart muscle cell; hematopoiesis; human; human cell; hypophysis cell; inflammation; knockout mouse; nervous system development; nonhuman; protein expression; protein family; protein function; regulatory mechanism; review; signal transduction; transgenic mouse; tumor; Animals; Cytokines; DNA-Binding Proteins; Humans; Neural Cell Adhesion Molecules; Protein-Tyrosine Kinases; Signal Transduction; STAT1 Transcription Factor; STAT3 Transcription Factor; Trans-Activators; Animalia; Janus; Mus musculus
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

Cytokines regulate many cellular responses such as proliferation, differentiation and survival and play regulatory roles in numerous organ systems. The cytokines of the IL-6 family use the membrane glycoprotein gp130 as a signal transducer and signal through the JAK/STAT pathway. As they share a common signal transducer they show some functional redundancy but also exhibit specific biological activities. Considering that gp130 is ubiquitously expressed, the time and place at which gp130 functions in vivo appears to be determined by spatially and chronologically regulated expression of specific cytokine-binding receptor chains or cytokines themselves. The study of transgenic and knock-out mice for different members of the gp130 signaling cascade has revealed they are critical in embryo development and play a role in physiological responses as diverse as hematopoiesis, the inflammatory response, nervous system development and survival and myocardial and pituitary proliferation. gp130 cytokines have also been implicated in cellular transformation and the pathophysiology of many tumors. Recently, two new families of proteins that function as negative regulators of cytokine signaling, SOCS and PIAS, have been extensively studied and could be new targets for the treatment of pathologies originated by gp130 signaling disregulation. The ubiquitin-proteosome pathway and the new ubiquitin-like protein SUMO-1 seem to play an important role in SOCS and PIAS mediated inhibition but the mechanisms still remain to be elucidated.
Fil:Carbia-Nagashima, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.