Ca2+-Calmodulin-dependent Protein Kinase II Potentiates Store-operated Ca2+ Current

Machaca, Khaled

doi:10.1074/jbc.m305023200

Cited by 31 publications

(23 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In turn, PLC␥ activation, Ca 2ϩ flux, and Erk activation were also reduced following TCR stimulation in cells that express active CaMKII. The decrease in Ca 2ϩ mobilization was not due to negative regulation of CRAC channels by CaMKII as it has been reported in a neuron cell line (36), because thymocytes from CaMKII␥B* mice responded to ionomycin with the same intensity as WT thymocytes, whether or not the medium contained extracellular free Ca 2ϩ . This work describes a previously unrecognized role of CaMKII in proximal TCR signaling.…”

Section: Discussionsupporting

confidence: 74%

Active Ca2+/Calmodulin-Dependent Protein Kinase IIγB Impairs Positive Selection of T Cells by Modulating TCR Signaling

McGargill

Sharp²,

Bui³

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

T cell development is regulated at two critical checkpoints that involve signaling events through the TCR. These signals are propagated by kinases of the Src and Syk families, which activate several adaptor molecules to trigger Ca2+ release and, in turn, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation. In this study, we show that a constitutively active form of CaMKII antagonizes TCR signaling and impairs positive selection of thymocytes in mice. Following TCR engagement, active CaMKII decreases TCR-mediated CD3ζ chain phosphorylation and ZAP70 recruitment, preventing further downstream events. Therefore, we propose that CaMKII belongs to a negative-feedback loop that modulates the strength of the TCR signal through the tyrosine phosphatase Src homology 2 domain-containing phosphatase 2 (SHP-2).

show abstract

Section: Discussionsupporting

confidence: 74%

Active Ca2+/Calmodulin-Dependent Protein Kinase IIγB Impairs Positive Selection of T Cells by Modulating TCR Signaling

McGargill

Sharp²,

Bui³

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…At the same time, the present data raise an interesting question regarding how Ca 2+ entry through the T-type Ca 2+ channel is coupled to the hCG-triggered intracellular signalling, thus modulating testosterone production. As previously suggested by others, store-operated Ca 2+ influx is one possibility [12,13]. The other possibility is that surface density or Ca +2 channel membrane activity is subjected to hCG signalling pathway effector proteins [28], possibly through phosphorylation, membrane trafficking or both.…”

Section: Discussionmentioning

confidence: 80%

“…Ca 2+ helps regulate a variety of cellular functions in many different cells, including germ cells and somatic cells in the testis, as well as spermatozoa, in response to endocrine hormones and local regulators [7][8][9][10][11]. Moreover, alteration of the Ca 2+ signalling pathway has a drastic impact on many cellular physiologies [12][13][14][15] [5,6,17], while other studies have argued that voltage-dependent Ca 2+ channels (VDCCs) are also involved [18][19][20]. Recently, mibefradil, a new nondihydropyridine calcium antagonist, has been shown to block the T-type Ca 2+ channel with a high affinity and selectivity in a variety of cell preparations [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory actions of mibefradil on steroidogenesis in mouse Leydig cells: involvement of Ca2+ entry via the T-type Ca2+ channel

Lee¹,

Kim²,

Kim³

et al. 2010

Asian J Androl

View full text Add to dashboard Cite

Intracellular cAMP and Ca 2+ are involved in the regulation of steroidogenic activity in Leydig cells, which coordinate responses to luteinizing hormone (LH) and human chorionic gonadotropin (hCG). However, the identification of Ca 2+ entry implicated in Leydig cell steroidogenesis is not well defined. The objective of this study was to identify the type of Ca 2+ channel that affects Leydig cell steroidogenesis. In vitro steroidogenesis in the freshly dissociated Leydig cells of mice was induced by hCG incubation. The effects of mibefradil (a putative T-type Ca 2+ channel blocker) on steroidogenesis were assessed using reverse transcription (RT)-polymerase chain reaction analysis for the steroidogenic acute regulatory protein (StAR) mRNA expression and testosterone production using radioimmunoassay. In the presence of 1.0 mmol L −1 extracellular Ca 2+ , hCG at 1 to 100 IU noticeably elevated both StAR mRNA level and testosterone secretion (P < 0.05), and the stimulatory effects of hCG were markedly diminished by mibefradil in a dose-dependent manner (P < 0.05). Moreover, the hCG-induced increase in testosterone production was completely removed when external Ca 2+ was omitted, implying that Ca 2+ entry is needed for hCG-induced steroidogenesis. Furthermore, a patch-clamp study revealed the presence of mibefradil-sensitive Ca 2+ currents seen at a concentration range that nearly paralleled those inhibiting steroidogenesis. Collectively, our data provide evidence that hCG-stimulated steroidogenesis is mediated at least in part by Ca 2+ entry carried out by the T-type Ca 2+ channel in the Leydig cells of mice.

show abstract

“…The pharmacology for these channels has not been clearly worked out as they comprise a large family that may form heterodimeric channels with greatly different pharmacologies and properties dependent upon the cell type [36]. They are also regulated to some extent by [Ca 2+ ] O in the physiological range of synaptic cleft Ca 2+ [33,37,38]. As observed in non-neuronal cells, re-addition of Ca 2+ activates CCE through these SOC and then regulates downstream Ca 2+ -signaling pathways.…”

Section: Camkii De-phosphorylation Is Regulated By Intracellular Stormentioning

confidence: 99%

“…As well, readdition of Ca 2+ O increases Ca 2+ i to a much higher level directly beneath the membrane than within the cytoplasm [42]. Other experimental systems have demonstrated that intracellular stores act to regulate CaMKII activation [43] and CaMKII acts to potentiate SOC currents [37].…”

Section: Store-operated Channels May Underlie An Important Influx Mecmentioning

confidence: 99%

CaMKII inactivation by extracellular Ca2+ depletion in dorsal root ganglion neurons

Cohen

Fields

2006

Cell Calcium

View full text Add to dashboard Cite

A mechanism by which Ca 2+ /CaM-dependent protein kinase (CaMKII) O has profound effects on intracellular Ca 2+ signaling and CaMKII autophosphorylation, in the absence of measurable changes in intracellular Ca 2+ . These findings have wide-ranging significance, because [Ca 2+ ] O is manipulated in many experimental studies. Moreover, this explanation for the paradoxical changes in CaMKII phosphorylation in response to manipulating [Ca 2+ ] O provides a possible mechanism linking activitydependent depletion of Ca 2+ from the synaptic cleft to a protein kinase regulating many neuronal properties.

show abstract

Ca2+-Calmodulin-dependent Protein Kinase II Potentiates Store-operated Ca2+ Current

Cited by 31 publications

References 39 publications

Active Ca2+/Calmodulin-Dependent Protein Kinase IIγB Impairs Positive Selection of T Cells by Modulating TCR Signaling

Active Ca2+/Calmodulin-Dependent Protein Kinase IIγB Impairs Positive Selection of T Cells by Modulating TCR Signaling

Inhibitory actions of mibefradil on steroidogenesis in mouse Leydig cells: involvement of Ca2+ entry via the T-type Ca2+ channel

CaMKII inactivation by extracellular Ca2+ depletion in dorsal root ganglion neurons

Contact Info

Product

Resources

About