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

Mol Cell Endocrinol. 2015 Jan 5;399:69-77. doi: 10.1016/j.mce.2014.08.010. Epub 2014 Aug 22.

Abstract

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 Ca(2+)/calmodulin dependent protein kinase, whereas the effect of Ig-like domains showed greater sensitivity to the inhibition of the adenylyl cyclase-cAMP-PKA pathway.

Keywords: Fn type III domain; Ig-like domain; Insulin-like growth factor 1; Mechano-growth factor; Myomesin; Titin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / drug effects*
  • Connectin / pharmacology*
  • Humans
  • Insulin-Like Growth Factor I / biosynthesis*
  • Insulin-Like Growth Factor I / genetics
  • Myoblasts / cytology
  • Myoblasts / metabolism*
  • Protein Structure, Tertiary
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics

Substances

  • Connectin
  • IGF1 protein, human
  • RNA, Messenger
  • TTN protein, human
  • Insulin-Like Growth Factor I