Premium
Maitotoxin, a calcium channel activator, inhibits cell cycle progression through the G1/S and G2/M transitions and prevents CDC2 kinase activation in GH 4 C 1 cells
Author(s) -
Van Dolah Frances M.,
Ramsdell John S.
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199601)166:1<49::aid-jcp6>3.0.co;2-g
Subject(s) - cyclin dependent kinase 1 , cell cycle , microbiology and biotechnology , mitosis , calcium channel , cyclin dependent kinase 2 , kinase , calcium in biology , activator (genetics) , t type calcium channel , calcium , chemistry , biology , intracellular , cell , protein kinase a , biochemistry , receptor , organic chemistry
Calcium regulates progression through several checkpoints in the cell cycle, including the G1/S‐phase transition, G2/M‐phase transition, and exit from mitosis. In the GH 4 C 1 rat pituitary cell line, calcium mobilizing polypeptides and calcium channel activation inhibit cell proliferation. This report examines the effects of maitotoxin (MTX), an activator of type L voltage‐dependent calcium channels (L‐VDCC), on calcium influx and cell cycle progression in GH 4 C 1 cells. MTX causes both a block from G1 to S‐phase and a concentration‐dependent accumulation of cells in G2+M. MTX does not increase the mitotic index; thus, sustained calcium channel activation by MTX results in an accumulation of cells in G2. In order to temporally localize the MTX‐induced G2 block relative to cell cycle regulatory events at the G2/M transition, we assessed the relative activity of two cell cycle regulatory protein kinases, CDC2 and CDK2, in MTX‐treated cells. CDC2‐specific histone kinase activity in MTX‐treated cells is lower than either in cells blocked in mitosis with the microtubule destabilizing agent demecolcine or in randomly cycling cells. In contrast, the activity of CDK2 is highest in MTX‐treated cells, consistent with a G2 block prior to CDC2 activation. Together, these results implicate calcium as an intracellular signal required for progression through G2 phase of the cell cycle prior to CDC2 kinase activation. © 1996 Wiley‐Liss, Inc.