Functional inactivation of the IGF-I receptor delays differentiation of skeletal muscle cells

Abstract

Skeletal myoblasts are inherently programmed to leave the cell cycle and begin the differentiation process following removal of exogenous growth factors. Serum withdrawal results in a marked induction of IGF production which is essential for skeletal muscle differentiation in vitro. However, the potential role of the tyrosine kinase IGF-I receptor (thought to be the principal mediator of both IGF-I and II signaling in skeletal muscle) in the decision of myoblasts to begin differentiation following serum withdrawal is unknown. To explore the role of the IGF-I receptor in this decision by skeletal myoblasts, we functionally inactivated endogenous IGF

Developmental changes and the impact of isoflavones on mRNA expression of IGF-I receptor, EGF receptor and related growth factors in porcine skeletal muscle cell cultures

“…Moreover, the IGF-I receptor expression during muscle cell differentiation may be regulated through autocrine production of IGF-II [34,35]. Functional inactivation of the IGF-I receptor caused a delay of differentiation in mouse skeletal muscle cells [36]. We found that IGF-I receptor mRNA expression tended to increase with differentiation in porcine muscle cell cultures.…”

IGF-I binding and receptor signal transduction in primary cell culture of muscle cells of gilthead sea bream: changes throughout in vitro development

“…Thus, the data reported in the present study suggest that increases in IGF-IR numbers and specific binding might be related to the differentiation of the primary gilthead sea bream myocytes. Indeed, functional inactivation of the IGF-IRs delays the differentiation of C2C12 muscle cells (Cheng et al 2000), whereas overexpression of IGF-IRs accelerates myogenic differentiation (Quinn et al 1994;Quinn and Haugk 1996).…”

“…IGFs are thought to stimulate muscle cell proliferation and differentiation in culture through interaction with the IGF-IR (Ewton et al 1987;Duclos et al 1991;Galvin et al 2003), thereby stimulating tyrosine kinase activity and the activation of the MAPK signalling pathway during proliferation (Coolican et al 1997) and differentiation (Wu et al 2000) in various cell in vitro model systems. In addition, this binding process activates the PI3K/Akt pathway during differentiation (Coolican et al 1997).…”

Cytokine-Hormone Interactions: Tumor Necrosis Factor α Impairs Biologic Activity and Downstream Activation Signals of the Insulin-Like Growth Factor I Receptor in Myoblasts

“…Introduction of a mutant type I IGF-I receptor that is unable to autophosphorylate reduces myoblast differentiation upon serum withdraw (40). Conversely, increasing expression of the type I IGF-I receptor promotes spontaneous differentiation of myoblasts (41).…”