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

Rodriguez-Mora, Oswaldo; LaHair, Michelle M.; McCubrey, James A.; Franklin, Richard A.

doi:10.1158/0008-5472.can-05-0271

Cited by 73 publications

(61 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Combined with these recent findings, our data are suggestive of the possibility that nuclear PTEN induces G 0 -G 1 cell cycle arrest by Ca 2+ signaling-regulated nuclear import. Ca 2+ signaling is known to regulate G 1 -S progression of the cell cycle through promoting phospholipase C/protein kinase C/MAPK and calmodulin (CaM)/ CaM-dependent kinase (CaM-K) kinase/CaM-K pathways (23)(24)(25)(26). Therefore, it is reasonable to postulate that Ca 2+ signaling is also regulating nuclear entry of PTEN, resulting in modulation of G 1 cell cycle arrest.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Localization of PTEN Is Regulated by Ca2+ through a Tyrosil Phosphorylation–Independent Conformational Modification in Major Vault Protein

2006

View full text Add to dashboard Cite

We have recently shown in MCF-7 cells that nuclear phosphatase and tensin homologue deleted on chromosome 10 (PTEN) down-regulates phosphorylation of p44/42 and cyclin D1 and induces G 1 cell cycle arrest, whereas cytoplasmic PTEN down-regulates phosphorylation of Akt, up-regulates p27, and induces apoptosis. In this manner, nucleocytoplasmic partitioning of PTEN seems to differentially regulate the cell cycle and apoptosis. We have also reported that PTEN has nuclear localization signal-like sequences required for major vault protein (MVP)-mediated nuclear translocation. To date, several other proteins are reported to interact with MVP, including extracellular signal-regulated kinases and steroid receptors, suggesting that MVP is likely to be involved in signal transduction through nucleocytoplasmic transport. However, the exact mechanism of MVP-mediated nucleocytoplasmic shuttling remains elusive. PTEN reportedly interacts in vitro with the EF hand-like motif of MVP in a Ca 2+ -dependent manner. The current study shows that small interfering RNA-mediated MVP silencing decreases the nuclear localization of PTEN and increases phosphorylation of nuclear p44/42. We show in situ that PTEN-MVP interaction is Ca 2+ dependent and is abolished by Mg 2+ . Nuclear localization of PTEN is decreased by increasing Ca 2+ levels in culture medium in a dose-dependent manner. Ca 2+ ionophore A23187 increases nuclear localization of PTEN and decreases phosphorylation of nuclear p44/42. Finally, we show that Ca 2+ -dependent PTEN-MVP interaction is not related to MVP's tyrosil phosphorylation but rather due to its conformational modification. Our observations suggest that Ca 2+ regulates PTEN's nuclear entry through a tyrosil phosphorylationindependent conformational change in MVP. Collectively, our data present evidence of a novel crosstalk between the Ca 2+ signaling-mediated regulation of the cell cycle and MVP-mediated nuclear PTEN localization and function.

show abstract

Section: Discussionmentioning

confidence: 99%

Nuclear Localization of PTEN Is Regulated by Ca2+ through a Tyrosil Phosphorylation–Independent Conformational Modification in Major Vault Protein

2006

View full text Add to dashboard Cite

show abstract

“…Since these inhibitors disrupt CaMKI and CaMKIV activities [32,33], and may therefore affect CKLiK activities in neutrophils, we tested whether KN-93 and the recently identified CaMKKα inhibitor STO-609 also affect the growth or functional responses of our cell lines. In agreement with previous studies on human leukemic cell lines, KN93 inhibited the growth of both EPRO and SCF ER-Hoxb8 cells in a dose dependent fashion (Fig.…”

Section: Effects Of Camk Inhibitors On Murine Neutrophil Growth Diffmentioning

confidence: 99%

A cascade of Ca2+/calmodulin-dependent protein kinases regulates the differentiation and functional activation of murine neutrophils

Gaines

Lamoureux

Marisetty

et al. 2008

Experimental Hematology

View full text Add to dashboard Cite

Objective-The function of neutrophils as primary mediators of innate immunity depends on the activity of granule proteins and critical components of the NADPH oxidase complex. Expression of their cognate genes is regulated during neutrophil differentiation by a complex network of intracellular signaling pathways. In this study we have investigated the role of two members of the calcium/calmodulin-dependent protein kinase (CaMK) signaling cascade, CaMKI-like kinase (CKLiK) and CaMKKα, in regulating neutrophil differentiation and functional activation.Materials and Methods-Mouse myeloid cell lines were used to examine the expression of a CaMK cascade in developing neutrophils and to examine the effects of constitutive activation versus inhibition of CaMKs on neutrophil maturation.Results-Expression of CaMKKα was shown to increase during neutrophil differentiation in multiple cell lines, whereas expression of CKLiK increased as multipotent progenitors committed to promyelocytes but then decreased as cells differentiated into mature neutrophils. Expression of constitutively active CKLiKs did not affect morphologic maturation, but caused dramatic decreases in both respiratory burst responses and chemotaxis. This loss of neutrophil function was accompanied by reduced secondary granule and gp91 phox gene expression. The CaMK inhibitor KN93 attenuated cytokine-stimulated proliferative responses in promyelocytic cell lines, and inhibited the respiratory burst. Similar data were observed with the CaMKKα inhibitor, STO-609.Conclusions-Overactivation of a cascade of CaMKs inhibits neutrophil maturation, suggesting that these kinases play an antagonistic role during neutrophil differentiation, but at least one CaMK is required for myeloid cell expansion and functional activation.

show abstract

“…KN-93, as a membrane permeant compound of CaMK Ⅱ-selective inhibitor, can intensively prevent CaMK-Ⅱ activation by antagonizing CaM binding [10] , and has been used in functional studies on living cells. In contrast to KN-93, KN-92 is a congener of KN-93 without CaM kinase inhibitory activity and has been used as an experimental control [11] . It was reported that KN-93 not only suppresses CaMKⅡ activity but is a strong inhibitor of cell proliferation [12] .…”

Section: Introductionmentioning

confidence: 99%

KN-93, a specific inhibitor of CaMKII inhibits human hepatic stellate cell proliferation бin vitro��

Zhu²,

Yang³

et al. 2007

WJG

View full text Add to dashboard Cite

AIM:To investigate the effects of KN-93, a CaMKⅡ selective inhibitor on cell proliferation and the expression of p53 or p21 protein in human hepatic stellate cells. METHODS:Human hepatic stellate cells (LX-2) were incubated with various concentrations (0-50 mmol/L) of KN-93 or its inactive derivative, KN-92. Cell proliferation was measured by CCK-8 assay, and the expression of two cell cycle regulators, p53 and p21, was determined by SDS-PAGE and Western blotting.RESULTS: K N -9 3 ( 5 -5 0 mm o l / L ) d e c r e a s e d t h e proliferation of human hepatic stellate cells in a dosedependent manner from 81.76% (81.76% ± 2.58% vs 96.63% ± 2.69%, P < 0.05) to 27.15% (27.15% ± 2.86% vs 96.59% ± 2.44%, P < 0.01) after 24 h treatment.Incubation of 10 mmol/L KN-93 induced the cell growth reduction in a time-dependent manner from 78.27% at 8 h to 11.48% at 48 h. However, KN-92, an inactive derivative of KN-93, did not inhibit cell proliferation effectively. Moreover, analysis of cell cycle regulator expression revealed that KN-93 rather than KN-92 reduced the expression of p53 and p21.CONCLUSION: KN-93 has potent inhibitory effect on proliferation of LX-2 cells by modulating the expression of two special cell cycle regulators, p53 and p21.

show abstract

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

Cited by 73 publications

References 47 publications

Nuclear Localization of PTEN Is Regulated by Ca2+ through a Tyrosil Phosphorylation–Independent Conformational Modification in Major Vault Protein

Nuclear Localization of PTEN Is Regulated by Ca2+ through a Tyrosil Phosphorylation–Independent Conformational Modification in Major Vault Protein

A cascade of Ca2+/calmodulin-dependent protein kinases regulates the differentiation and functional activation of murine neutrophils

KN-93, a specific inhibitor of CaMKII inhibits human hepatic stellate cell proliferation бin vitro��

Contact Info

Product

Resources

About