RGC-32 increases p34CDC2 kinase activity and entry of aortic smooth muscle cells into S-phase

J Biol Chem. 2002 Jan 4;277(1):502-8. doi: 10.1074/jbc.M109354200. Epub 2001 Oct 30.

Abstract

Proliferation of aortic smooth muscle cells contributes to atherogenesis and neointima formation. Sublytic activation of complement, particularly C5b-9, induces cell cycle progression in aortic smooth muscle cells. RGC-32 is a novel protein that may promote cell cycle progression in response to complement activation. We cloned human RGC-32 cDNA from a human fetal brain cDNA library. The human RGC-32 cDNA encodes a 117-amino acid protein with 92% similarity to the rat and mouse protein. Human RGC-32 maps to chromosome 13 and is expressed in most tissues. Sublytic complement activation enhanced RGC-32 mRNA expression in human aortic smooth muscle cells and induced nuclear translocation of the protein. RGC-32 was physically associated with cyclin-dependent kinase p34CDC2 and increased the kinase activity in vivo and in vitro. In addition, RGC-32 was phosphorylated by p34CDC2-cyclin B1 in vitro. Mutation of RGC-32 protein at Thr-91 prevented the p34CDC2-mediated phosphorylation and resulted in loss of p34CDC2 kinase enhancing activity. Overexpression of RGC-32 induced quiescent aortic smooth muscle cells to enter S-phase. These data indicate that cell cycle activation by C5b-9 may involve p34CDC2 activity through RGC-32. RGC-32 appears to be a cell cycle regulatory factor that mediates cell proliferation, both as an activator and substrate of p34CDC2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Sequence
  • Animals
  • Aorta / cytology*
  • Base Sequence
  • CDC2 Protein Kinase / biosynthesis*
  • Cell Cycle Proteins*
  • Chromosome Mapping
  • Cloning, Molecular
  • Complement System Proteins / physiology
  • Humans
  • Mice
  • Molecular Sequence Data
  • Muscle Proteins*
  • Muscle, Smooth, Vascular / cytology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Phosphorylation
  • RNA, Messenger / analysis
  • S Phase

Substances

  • Cell Cycle Proteins
  • Muscle Proteins
  • Nerve Tissue Proteins
  • RGCC protein, human
  • RNA, Messenger
  • Rgcc protein, rat
  • Complement System Proteins
  • CDC2 Protein Kinase

Associated data

  • GENBANK/AF036549