Induction of insulin-like growth factor 1 splice forms by subfragments of myofibrillar proteins

• Subfragments of titin and myomesin composed of Fn type III and Ig-like domains can activate IGF-1 and MGF expression in cultured myoblasts.
• Each of the domain-type, Ig or Fn III, binds to its own receptor on the myoblast membrane and do not compete with domains of another class.
• The effect of Fn type III domains is more sensitive to inhibition of Ca2+/calmodulin dependent protein kinase activity, whereas the effect of Ig-like domains shows greater sensitivity to the inhibition of the adenylyl cyclase–cAMP–PKA pathway.

Expression of insulin-like growth factor 1 (IGF-1) mRNAs splice forms was recently shown to be stimulated by myofibrillar proteins released from the damaged muscle. In this study, we report that individual subfragments of titin and myomesin composed of Fn type III and Ig-like domains can activate expression of two IGF-1 splice forms in cultured myoblasts, both at protein and mRNA levels. Competition studies showed that each of the domain-types interacts with its own receptor. Induction of IGF-1 expression caused by domains of different types showed dissimilar sensitivity to inhibitors of regulatory cascades. The effect of Fn type III domains was more sensitive to inhibition of Ca2+/calmodulin dependent protein kinase, whereas the effect of Ig-like domains showed greater sensitivity to the inhibition of the adenylyl cyclase–cAMP–PKA pathway.