The roles of protein kinase C beta I and beta II in vascular smooth muscle cell proliferation.
The role of protein kinase C (PKC) on proliferation of A10 vascular smooth muscle cells (VSMC) was studied by overexpressing specific PKC-beta I and -beta II isozymes. PKC-beta I and -beta II are derived from alternative splicing of the exon encoding the carboxy-terminal (C-terminal) 50 or 52 amino acids, respectively. The differential functions of the two isozymes with regard to cell proliferation, DNA synthesis, and the cell cycle were investigated in A10 cells, a clonal cell line of VSMC from rat aorta, and in A10 cells overexpressing PKC-beta I and PKC-beta II (beta I-A10 and beta II-A10). PKC levels were increased three- to fourfold in heterogeneous cultures of stably transfected cells. Although doubling time of A10 cells was 36 h, the cell doubling time in beta I-A10 cells decreased by 12 h, and, in contrast, the doubling time of beta II-A10 cells increased by 12 h compared to A10 cells. The increase of [3H]thymidine (TdR) incorporation was accelerated and increased in beta I-A10 cells, but slowed and diminished in beta II-A10 cells compared to A10 and control cells transfected with empty vector. Cell cycle analysis of beta I-A10 cells showed an acceleration of S phase entry while beta II-A10 cells slowed S phase entry. These results suggest that PKC-beta I and PKC-beta II regulate cell proliferation bidirectionally and that PKC-beta I and PKC-beta II may have distinct and opposing functions as cell cycle check point mediators during late G1 phase and may regulate S phase entry in A10 VSMC.
Yamamoto
M
M
Department of Biochemistry and Molecular Biology, University of South Florida College of Medicine, Tampa, USA. myamamot@com1.med.usf.edu
Acevedo-Duncan
M
M
Chalfant
C E
CE
Patel
N A
NA
Watson
J E
JE
Cooper
D R
DR
D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D015870:Gene Expression; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology*; D064546:Protein Kinase C beta; D051381:Rats
D007527:Isoenzymes; D011493:Protein Kinase C; D064546:Protein Kinase C beta