CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tombes, R. M.
Right arrow Articles by Krystal, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tombes, R. M.
Right arrow Articles by Krystal, G.

Cell Growth & Differentiation, Vol 6, Issue 9 1063-1070, Copyright © 1995 by American Association of Cancer Research


ARTICLES

G1 cell cycle arrest and apoptosis are induced in NIH 3T3 cells by KN-93, an inhibitor of CaMK-II (the multifunctional Ca2+/CaM kinase)

RM Tombes, S Grant, EH Westin and G Krystal
Division of Hematology and Oncology, Medical College of Virginia, Richmond, USA.

CaMK-II (the type II multifunctional Ca2+/calmodulin kinase) is a ubiquitous serine/threonine protein kinase that is activated by Ca2+ and calmodulin (CaM) and has been implicated in cell cycle control. NIH 3T3 fibroblast cytosolic extracts contain CaMK-II enzymatic activity and two major Ca2+/CaM-dependent phosphoproteins of M(r) 55,000 and 115,000. Reverse transcription-PCR indicates that the gamma B and gamma C isozymes of CaMK-II are predominately expressed. KN-93, a novel membrane-permeant synthetic inhibitor of purified neuronal CaMK-II, inhibits serum-induced fibroblast cell growth in a comparable dose-dependent fashion to its inhibition of CaMK-II activity. After 2 days of KN-93 treatment, 95% of cells are arrested in G1. G1 arrest is reversible; 1 day after KN-93 release, a peak of cells had progressed into S and G2-M. KN-92, a similar but inactive compound, had no effect on CaMK-II activity or cell growth. KN-93 also blocked cell growth stimulated by basic fibroblast growth factor, platelet-derived growth factor-BB, epidermal growth factor, and insulin-like growth factor-1. After 3 days of KN-93-induced G1 arrest, cell size and viability decreased and DNA fragmented, indicating apoptosis. These data suggest that CaMK-II is necessary for cell cycle progression through G1 and operates at a site common to the transduction of signals from growth and/or survival factors.


This article has been cited by other articles:


Home page
J Biol ChemHome page
D. Chiluiza, S. Krishna, V. A. Schumacher, and J. Schlondorff
Gain-of-function Mutations in Transient Receptor Potential C6 (TRPC6) Activate Extracellular Signal-regulated Kinases 1/2 (ERK1/2)
J. Biol. Chem., June 21, 2013; 288(25): 18407 - 18420.
[Abstract] [Full Text] [PDF]


Home page
J. Neurosci.Home page
C. T. Waggener, J. L. Dupree, Y. Elgersma, and B. Fuss
CaMKII{beta} Regulates Oligodendrocyte Maturation and CNS Myelination
J. Neurosci., June 19, 2013; 33(25): 10453 - 10458.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
X.-D. He and R. K. Goyal
CaMKII inhibition hyperpolarizes membrane and blocks nitrergic IJP by closing a Cl- conductance in intestinal smooth muscle
Am J Physiol Gastrointest Liver Physiol, July 15, 2012; 303(2): G240 - G246.
[Abstract] [Full Text] [PDF]


Home page
Biol. Reprod.Home page
K. C. W. Wang, D. A. Brooks, K. J. Botting, and J. L. Morrison
IGF-2R-Mediated Signaling Results in Hypertrophy of Cultured Cardiomyocytes from Fetal Sheep
Biol Reprod, June 22, 2012; 86(6): 183 - 183.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
S. C. Rothschild, L. Francescatto, I. A. Drummond, and R. M. Tombes
CaMK-II is a PKD2 target that promotes pronephric kidney development and stabilizes cilia
Development, August 15, 2011; 138(16): 3387 - 3397.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Cell Physiol.Home page
A. Becchetti
Ion channels and transporters in cancer. 1. Ion channels and cell proliferation in cancer
Am J Physiol Cell Physiol, August 1, 2011; 301(2): C255 - C265.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
W. Li, H. Li, P. N. Sanders, P. J. Mohler, J. Backs, E. N. Olson, M. E. Anderson, and I. M. Grumbach
The Multifunctional Ca2+/Calmodulin-dependent Kinase II {delta} (CaMKII{delta}) Controls Neointima Formation after Carotid Ligation and Vascular Smooth Muscle Cell Proliferation through Cell Cycle Regulation by p21
J. Biol. Chem., March 11, 2011; 286(10): 7990 - 7999.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
L. Francescatto, S. C. Rothschild, A. L. Myers, and R. M. Tombes
The activation of membrane targeted CaMK-II in the zebrafish Kupffer's vesicle is required for left-right asymmetry
Development, August 15, 2010; 137(16): 2753 - 2762.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
N. Guetg, S. A. Aziz, N. Holbro, R. Turecek, T. Rose, R. Seddik, M. Gassmann, S. Moes, P. Jenoe, T. G. Oertner, et al.
NMDA receptor-dependent GABAB receptor internalization via CaMKII phosphorylation of serine 867 in GABAB1
PNAS, August 3, 2010; 107(31): 13924 - 13929.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
R. Waldsee, H. Ahnstedt, S. Eftekhari, and L. Edvinsson
Involvement of calcium-calmodulin-dependent protein kinase II in endothelin receptor expression in rat cerebral arteries
Am J Physiol Heart Circ Physiol, February 24, 2010; 298(3): H823 - H832.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
S. Ma, Y. Yang, C. Wang, N. Hui, L. Gu, H. Zhong, Z. Cai, Q. Wang, Q. Zhang, N. Li, et al.
Endogenous Human CaMKII Inhibitory Protein Suppresses Tumor Growth by Inducing Cell Cycle Arrest and Apoptosis through Down-regulation of the Phosphatidylinositide 3-Kinase/Akt/HDM2 Pathway
J. Biol. Chem., September 11, 2009; 284(37): 24773 - 24782.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
J. Si and S. J. Collins
Activated Ca2+/Calmodulin-Dependent Protein Kinase II{gamma} Is a Critical Regulator of Myeloid Leukemia Cell Proliferation
Cancer Res., May 15, 2008; 68(10): 3733 - 3742.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
C. Wang, N. Li, X. Liu, Y. Zheng, and X. Cao
A Novel Endogenous Human CaMKII Inhibitory Protein Suppresses Tumor Growth by Inducing Cell Cycle Arrest via p27 Stabilization
J. Biol. Chem., April 25, 2008; 283(17): 11565 - 11574.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Cell Physiol.Home page
S. J. House, R. G. Ginnan, S. E. Armstrong, and H. A. Singer
Calcium/calmodulin-dependent protein kinase II-{delta} isoform regulation of vascular smooth muscle cell proliferation
Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2276 - C2287.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
A. Perfetti, F. Oriente, S. Iovino, A. T. Alberobello, A. P. M. Barbagallo, I. Esposito, F. Fiory, R. Teperino, P. Ungaro, C. Miele, et al.
Phorbol Esters Induce Intracellular Accumulation of the Anti-apoptotic Protein PED/PEA-15 by Preventing Ubiquitinylation and Proteasomal Degradation
J. Biol. Chem., March 23, 2007; 282(12): 8648 - 8657.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
J. E. Rooney, J. V. Welser, M. A. Dechert, N. L. Flintoff-Dye, S. J. Kaufman, and D. J. Burkin
Severe muscular dystrophy in mice that lack dystrophin and {alpha}7 integrin
J. Cell Sci., June 1, 2006; 119(11): 2185 - 2195.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
L. Tang, P. K. Shukla, L. X. Wang, and Z. J. Wang
Reversal of Morphine Antinociceptive Tolerance and Dependence by the Acute Supraspinal Inhibition of Ca2+/Calmodulin-Dependent Protein Kinase II
J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 901 - 909.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
O. G. Rodriguez-Mora, M. M. LaHair, J. A. McCubrey, and R. A. Franklin
Calcium/Calmodulin-Dependent Kinase I and Calcium/Calmodulin-Dependent Kinase Kinase Participate in the Control of Cell Cycle Progression in MCF-7 Human Breast Cancer Cells
Cancer Res., June 15, 2005; 65(12): 5408 - 5416.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
W. Xiao, Y. Liu, and D. M. Templeton
Ca2+/calmodulin-dependent protein kinase II inhibition by heparin in mesangial cells
Am J Physiol Renal Physiol, December 6, 2004; 288(1): F142 - F149.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
B. P. Harvey, S. S. Banga, and H. L. Ozer
Regulation of the Multifunctional Ca2+/Calmodulin-dependent Protein Kinase II by the PP2C Phosphatase PPM1F in Fibroblasts
J. Biol. Chem., June 4, 2004; 279(23): 24889 - 24898.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
C. R. Kahl and A. R. Means
Regulation of Cyclin D1/Cdk4 Complexes by Calcium/Calmodulin-dependent Protein Kinase I
J. Biol. Chem., April 9, 2004; 279(15): 15411 - 15419.
[Abstract] [Full Text] [PDF]


Home page
Biol. Reprod.Home page
H.-Y. Fan, L.-J. Huo, X.-Q. Meng, Z.-S. Zhong, Y. Hou, D.-Y. Chen, and Q.-Y. Sun
Involvement of Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) in Meiotic Maturation and Activation of Pig Oocytes
Biol Reprod, November 1, 2003; 69(5): 1552 - 1564.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
M. M. Muthalif, N. A. Karzoun, I. F. Benter, L. Gaber, F. Ljuca, M. R. Uddin, Z. Khandekar, A. Estes, and K. U. Malik
Functional Significance of Activation of Calcium/Calmodulin-Dependent Protein Kinase II in Angiotensin II-Induced Vascular Hyperplasia and Hypertension
Hypertension, February 1, 2002; 39(2): 704 - 709.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
K. M. L. Tan, S.-L. Chan, K. O. Tan, and V. C. Yu
The Caenorhabditis elegansSex-determining Protein FEM-2 and Its Human Homologue, hFEM-2, Are Ca2+/Calmodulin-dependent Protein Kinase Phosphatases That Promote Apoptosis
J. Biol. Chem., November 23, 2001; 276(47): 44193 - 44202.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
Y. C. Sohn, E. Kwak, Y. Na, J. W. Lee, and S.-K. Lee
Silencing Mediator of Retinoid and Thyroid Hormone Receptors and Activating Signal Cointegrator-2 as Transcriptional Coregulators of the Orphan Nuclear Receptor Nur77
J. Biol. Chem., November 23, 2001; 276(47): 43734 - 43739.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
M. Kruidering, T. Schouten, G. I. Evan, and E. Vreugdenhil
Caspase-mediated Cleavage of the Ca2+/Calmodulin-dependent Protein Kinase-like Kinase Facilitates Neuronal Apoptosis
J. Biol. Chem., October 19, 2001; 276(42): 38417 - 38425.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
M. M. Muthalif, F. Ljuca, J. B. Roaten, N. Pentapaty, M. R. Uddin, and K. U. Malik
Ca2+/Calmodulin-Dependent Protein Kinase II and Cytosolic Phospholipase A2 Contribute to Mitogenic Signaling in Myeloblastic Leukemia U-937 Cells
J. Pharmacol. Exp. Ther., July 1, 2001; 298(1): 272 - 278.
[Abstract] [Full Text]


Home page
J Biol ChemHome page
M. K. Jang, Y. H. Goo, Y. C. Sohn, Y. S. Kim, S.-K. Lee, H. Kang, J. Cheong, and J. W. Lee
Ca2+/Calmodulin-dependent Protein Kinase IV Stimulates Nuclear Factor-{kappa}B Transactivation via Phosphorylation of the p65 Subunit
J. Biol. Chem., June 8, 2001; 276(23): 20005 - 20010.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
J. D. Joseph and A. R. Means
Identification and Characterization of Two Ca2+/CaM-dependent Protein Kinases Required for Normal Nuclear Division in Aspergillus nidulans
J. Biol. Chem., December 8, 2000; 275(49): 38230 - 38238.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
M. E. Anderson, A. P. Braun, Y. Wu, T. Lu, Y. Wu, H. Schulman, and R. J. Sung
KN-93, an Inhibitor of Multifunctional Ca++/Calmodulin-Dependent Protein Kinase, Decreases Early Afterdepolarizations in Rabbit Heart
J. Pharmacol. Exp. Ther., December 1, 1998; 287(3): 996 - 1006.
[Abstract] [Full Text]


Home page
J Biol ChemHome page
K. M. McGinnis, M. M. Whitton, M. E. Gnegy, and K. K. W. Wang
Calcium/Calmodulin-dependent Protein Kinase IV Is Cleaved by Caspase-3 and Calpain in SH-SY5Y Human Neuroblastoma Cells Undergoing Apoptosis
J. Biol. Chem., August 7, 1998; 273(32): 19993 - 20000.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
M. T. Ramirez, X.-L. Zhao, H. Schulman, and J. H. Brown
The Nuclear {delta}B Isoform of Ca2+/Calmodulin-dependent Protein Kinase II Regulates Atrial Natriuretic Factor Gene Expression in Ventricular Myocytes
J. Biol. Chem., December 5, 1997; 272(49): 31203 - 31208.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
M. I. Colombo, W. Beron, and P. D. Stahl
Calmodulin Regulates Endosome Fusion
J. Biol. Chem., March 21, 1997; 272(12): 7707 - 7712.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
J. D. Joseph and A. R. Means
Identification and Characterization of Two Ca2+/CaM-dependent Protein Kinases Required for Normal Nuclear Division in Aspergillus nidulans
J. Biol. Chem., December 8, 2000; 275(49): 38230 - 38238.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
M. K. Jang, Y. H. Goo, Y. C. Sohn, Y. S. Kim, S.-K. Lee, H. Kang, J. Cheong, and J. W. Lee
Ca2+/Calmodulin-dependent Protein Kinase IV Stimulates Nuclear Factor-{kappa}B Transactivation via Phosphorylation of the p65 Subunit
J. Biol. Chem., June 8, 2001; 276(23): 20005 - 20010.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1995 by the American Association of Cancer Research.