Nuclear factor kappa B-inducing kinase and Ikappa B kinase-alpha signal skeletal muscle cell differentiation

J Biol Chem. 2001 Jun 8;276(23):20228-33. doi: 10.1074/jbc.M100718200. Epub 2001 Mar 28.

Abstract

Nuclear factor kappaB (NF-kappaB)-inducing kinase (NIK), IkappaB kinase (IKK)-alpha and -beta, and IkappaBalpha are common elements that signal NF-kappaB activation in response to diverse stimuli. In this study, we analyzed the role of this pathway during insulin-like growth factor II (IGF-II)-induced myoblast differentiation. L6E9 myoblasts differentiated with IGF-II showed an induction of NF-kappaB DNA-binding activity that correlated in time with the activation of IKKalpha, IKKbeta, and NIK. Moreover, the activation of IKKalpha, IKKbeta, and NIK by IGF-II was dependent on phosphatidylinositol 3-kinase, a key regulator of myogenesis. Adenoviral transduction with the IkappaBalpha(S32A/S36A) mutant severely impaired both IGF-II-dependent NF-kappaB activation and myoblast differentiation, indicating that phosphorylation of IkappaBalpha at Ser-32 and Ser-36 is an essential myogenic step. Adenoviral transfer of wild-type or kinase-deficient forms of IKKalpha or IKKbeta revealed that IKKalpha is required for IGF-II-dependent myoblast differentiation, whereas IKKbeta is not essential for this process. Finally, overexpression of kinase-proficient wild-type NIK showed that the activation of NIK is sufficient to generate signals that trigger myogenin expression and multinucleated myotube formation in the absence of IGF-II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation* / drug effects
  • Cell Line
  • Enzyme Induction
  • I-kappa B Kinase
  • Insulin-Like Growth Factor II / pharmacology
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / enzymology
  • NF-kappaB-Inducing Kinase
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / metabolism*
  • Rats

Substances

  • Insulin-Like Growth Factor II
  • Protein Serine-Threonine Kinases
  • I-kappa B Kinase