CaMKIIdelta subtypes: localization and function

Gray, Charles B.B.; Brown, Joan Heller

doi:10.3389/fphar.2014.00015

Cited by 75 publications

(76 citation statements)

References 57 publications

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“…Third, there are four major isoforms of CaMKII, with each isoform group containing multiple sub- groups. Major differences in the properties of the isoforms have been reported, which can influence the role of the enzyme in the failing heart (11,41). Downregulation of SERCA2a expression is a common feature of most models of heart failure, with some reporting either an increase or no change in phospholamban content (24, 26 -28).…”

Section: Discussionmentioning

confidence: 99%

Role of protein phosphorylation in excitation-contraction coupling in taurine deficient hearts

Ramila

Jong

Pastukh

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Section: Discussionmentioning

confidence: 99%

Role of protein phosphorylation in excitation-contraction coupling in taurine deficient hearts

Ramila

Jong

Pastukh

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…Although many CaMK2 genes are widely expressed in a tissue-specific manner (29), the CaMK2D gene immediately caught our attention, because we had previously shown that CEACAM1-transfected cells specifically expressed CaMK2D during lumen formation (17) and that CaMK2D was associated with induction of apoptosis in ischemic cardiomyocytes (30). Notably, apoptosis is a central feature of lumen formation (6).…”

Section: Discussionmentioning

confidence: 99%

Induction of Lumen Formation in a Three-dimensional Model of Mammary Morphogenesis by Transcriptional Regulator ID4

Shively

2016

Journal of Biological Chemistry

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Concomitant loss of lumen formation and cell adhesion protein CEACAM1 is a hallmark feature of breast cancer. In a threedimensional culture model, transfection of CEACAM1 into MCF7 breast cells can restore lumen formation by an unknown mechanism. ID4, a transcriptional regulator lacking a DNA binding domain, is highly up-regulated in CEACAM1-transfected MCF7 cells, and when down-regulated with RNAi, abrogates lumen formation. Conversely, when MCF7 cells, which fail to form lumena in a three-dimensional culture, are transfected with ID4, lumen formation is restored, demonstrating that ID4 may substitute for CEACAM1. After showing the ID4 promoter is hypermethylated in MCF7 cells but hypomethylated in MCF/ CEACAM1 cells, ID4 expression was induced in MCF7 cells by agents affecting chromatin remodeling and methylation. Mechanistically, CaMK2D was up-regulated in CEACAM1-transfected cells, effecting phosphorylation of HDAC4 and its sequestration in the cytoplasm by the adaptor protein 14-3-3. CaMK2D also phosphorylates CEACAM1 on its cytoplasmic domain and mutation of these phosphorylation sites abrogates lumen formation. Thus, CEACAM1 is able to maintain the active transcription of ID4 by an epigenetic mechanism involving HDAC4 and CaMK2D, and the same kinase enables lumen formation by CEACAM1. Because ID4 can replace CEACAM1 in parental MCF7 cells, it must act downstream from CEACAM1 by inhibiting the activity of other transcription factors that would otherwise prevent lumen formation. This overall mechanism may be operative in other cancers, such as colon and prostate, where the down-regulation of CEACAM1 is observed.Lumen formation, a central feature of mammary morphogenesis, is lost during mammary tumorigenesis, starting with filling in the lumen with cancer cells in ductal carcinoma in situ (1) and becoming more evident in invasive solid tumors (2). Identification of the molecules that change during this process and the underlying mechanisms causing these changes are major goals of breast cancer research. Among the many molecules identified so far, CEACAM1 stands out as a luminal expressed protein that is rapidly down-regulated in both ductal carcinoma in situ (3) and invasive breast cancer (2). Not surprisingly, luminal expression of CEACAM1 occurs throughout ductal tissues such as the liver, digestive and urogenital tract, and prostate, and its loss upon malignant transformation is one of the earliest events observed (4). To study its role in lumen formation, we originally placed MCF10F, a cell line that expresses CEACAM1, in a three-dimensional culture system pioneered by Bissell and co-workers (5), and observed lumen formation with CEACAM1 at the luminal surface (3). When its expression was blocked by antisense, anti-CEACAM1 antibody, or peptides derived from the N terminus of CEACAM1, lumen formation was abrogated, demonstrating that its expression played a central role in the complex process of lumenogenesis (3). As a next step, we demonstrated that MCF7 breast cancer cells that fail to express CEACAM1 o...

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“…These 3 subtypes of CaMKIIδ have different subcellular localization and exert different effects [27]. Importantly, the ratio changes of CaMKIIδ isoforms could regulate the localization of the holoenzyme [28]. Therefore, the dysregulation of CaMKIIδ alternative splicing is involved in the pathogenesis of cardiac hypertrophy and heart failure [3,4].…”

Section: Discussionmentioning

confidence: 99%

Dyrk1A-ASF-CaMKIIδ Signaling Is Involved in Valsartan Inhibition of Cardiac Hypertrophy in Renovascular Hypertensive Rats

Yao

Qin²,

Zhu³

et al. 2015

Cardiology

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Objectives: It is known that the expression, activity and alternative splicing of Ca²⁺/calmodulin-dependent protein kinase IIδ (CaMKIIδ) are dysregulated in the cardiac remodeling process. Recently, we found a further signaling pathway, by which dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) regulates the alternative splicing of CaMKIIδ via the alternative splicing factor (ASF), i.e. Dyrk1A-ASF-CaMKIIδ. In this study, we aimed to investigate whether Dyrk1A-ASF-CaMKIIδ signaling was involved in valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats. Methods: Rats were subjected to two kidney-one clip (2K1C) surgery and then treated with valsartan (30 mg/kg/day) for 8 weeks. Hypertrophic parameter analysis was then performed. Western blot analysis was used to determine the protein expression of Dyrk1A and ASF and RT-PCR was used to analyze the alternative splicing of CaMKIIδ in the left ventricular (LV) sample. Results: Valsartan attenuated cardiac hypertrophy in 2K1C rats but without impairment of cardiac systolic function. Increased protein expression of Dyrk1A and decreased protein expression of ASF were observed in the LV sample of 2K1C rats. Treatment of 2K1C rats with valsartan reversed the changes in Dyrk1A and ASF expression in the LV sample. Valsartan adjusted the 2K1C-induced imbalance in alternative splicing of CaMKIIδ by upregulating the mRNA expression of CaMKIIδC and downregulating the mRNA expression of CaMKIIδA and CaMKIIδB. Conclusions: Valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats was mediated, at least partly, by Dyrk1A-ASF-CaMKIIδ signaling.

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CaMKIIdelta subtypes: localization and function

Cited by 75 publications

References 57 publications

Role of protein phosphorylation in excitation-contraction coupling in taurine deficient hearts

Role of protein phosphorylation in excitation-contraction coupling in taurine deficient hearts

Induction of Lumen Formation in a Three-dimensional Model of Mammary Morphogenesis by Transcriptional Regulator ID4

Dyrk1A-ASF-CaMKIIδ Signaling Is Involved in Valsartan Inhibition of Cardiac Hypertrophy in Renovascular Hypertensive Rats

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