IL-6 is a multifunctional cytokine involved in hemopoiesis, immune regulation, inflammation, neural development, and infection. IL-6 belongs to a family of related cytokines that includes leukemia inhibitory factor, oncostatin M, IL-11, ciliary neurotropic factor, and cardiotropin-1, all of which initiate signaling through a receptor-associated gp130. IL-6 induces homodimerization of gp130 and activates the Jak/STAT pathway of signal transduction. In addition, IL-6 stimulates the mitogen-activated protein kinases designated ERK (extracellular signal-regulated kinase)-1 and -2. Activation of ERK-1 and -2 may involve the Src homology-2 containing proteins Shc and Grb2. Here we provide evidence that Shc could function as signaling molecules for IL-6 in DeFew-IL-6R/gp130 cells, a human B lymphoma cell line engineered to express high levels of both the IL-6R (p80) and the gp130 subunit. IL-6 was shown to promote the rapid tyrosine phosphorylation of gp130, Jak2, and Shc proteins. Moreover, Shc associated both in vivo and in vitro with phosphorylated gp130 through the Shc-Src homology-2 domain. We also report that Shc bound to activated Jak2 by using the Shc amino terminal phosphotyrosine interaction domain. Following IL-6 stimulation, Shc physically associated with Grb2. Thus, the data point to Shc proteins as a functional link between the Jak2 and Ras pathways of IL-6 signal transduction.
|Titolo:||Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase|
|Parole Chiave:||Phosphotyrosine; Janus Kinase 2; Membrane Glycoproteins; DNA-Binding Proteins; Humans; STAT3 Transcription Factor; Protein-Tyrosine Kinases; Adaptor Proteins, Vesicular Transport; src Homology Domains; Receptors, Interleukin-6; Receptors, Interleukin; Cytokine Receptor gp130; Shc Signaling Adaptor Proteins; Proto-Oncogene Proteins; Phosphorylation; Adaptor Proteins, Signal Transducing; Antigens, CD; GRB2 Adaptor Protein; Proteins; Interleukin-6; Trans-Activators; Signal Transduction|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||1-mag-1997|
|Appare nelle tipologie:||01 - Articolo su periodico|