33 research outputs found
Avian sarcoma virus-transforming protein, pp60src shows protein kinase activity specific for tyrosine
Rous sarcoma virus transforming protein, p60src, expressed in E. coli, functions as a protein kinase
Microsatellite instability in the insulin–like growth factor II receptor gene in gastrointestinal tumours
Rous sarcoma virus-induced phosphorylation of a 50,000-molecular weight cellular protein
c-Src and IL-6 inhibit osteoblast differentiation and integrate IGFBP5 signalling
Interleukin-6 (IL-6) and c-Src impair osteoblast maturation in vitro and in vivo. Given the similar effects of these factors, they are likely to establish a functional loop to maintain osteoblasts in a less mature status. Here we describe a pathway whereby c-Src stimulates IL-6 expression through the STAT3 factor, which, in response to IL-6 induces insulin-like growth factor 5 (IGFBP5), a c-Src activating factor that amplifies this loop only in immature osteoblasts. In contrast, in mature osteoblasts, IGFBP5 is enhanced by Runx2, but is no longer able to stimulate c-Src activation, as this tyrosine kinase at this stage is downregulated. We find that the IGFBP5 produced by osteoblasts stimulates osteoclastogenesis and bone resorption, acting as an osteoblast-osteoclast coupling factor. Finally, we demonstrate that the integrated actions of c-Src, IL-6 and IGFBP5 also have a role in vivo. We conclude that this pathway is relevant for bone metabolism, both in physiological and in pathological conditions