RGC-32 increases p34CDC2 kinase activity and entry of aortic smooth muscle cells into S-phase.
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.
Badea
Tudor
T
University of Maryland School of Medicine, the Department of Pathology, Baltimore, Maryland 21201, USA.
Niculescu
Florin
F
Soane
Lucian
L
Fosbrink
Matthew
M
Sorana
Hila
H
Rus
Violeta
V
Shin
Moon L
ML
Rus
Horea
H
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000166:cytology*; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000096:biosynthesis*; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003165:Complement System Proteins / Q000502:physiology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D016196:S Phase
D018797:Cell Cycle Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C115049:RGCC protein, human; D012333:RNA, Messenger; C486417:Rgcc protein, rat; D003165:Complement System Proteins; D016203:CDC2 Protein Kinase