Disease relevance of CAMK1D

• CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo [1].
• The caM kinase, Pnck, is spatially and temporally regulated during murine mammary gland development and may identify an epithelial cell subtype involved in breast cancer [2].
• The human CaMKK, which was expressed as a Flag-tagged protein in human non-small cell lung cancer H- 1299 cells followed by immunoprecipitation with anti-Flag antibody, was shown to phosphorylate recombinant human CaMK I in a calcium/CaM-dependent fashion [3].
• These results indicated that CaMK II regulates c-FLIP expression and phosphorylation, thus modulating Fas-mediated signaling in glioma cells [4].
• METHODS: The previously unknown complete coding sequences of human CaMK IIbeta and the kinase domain of CaMK IIdelta were cloned from a human insulinoma cDNA library [5].

Psychiatry related information on CAMK1D

• The present study correlated the increased locomotor activity following ischemic insult with alterations in CaM kinase mRNA levels and immunocytochemical labeling of alpha and beta CaM kinase subunits in the hippocampus [6].
• In this review, we demonstrate the biologic behavior of seven novel molecules (Plks, Eph/ephrin, Id family, CaMK, c-Ets1, Elf-1, and survivin) in the endometrial carcinoma [7].

High impact information on CAMK1D

• This pathway could provide an interface between the potentiation of Ca2+ signals by CaM kinase and longer-term modifications of neuronal gene expression [8].
• Widespread localization, responsiveness to numerous signal transduction systems, and broad substrate specificity enable the multifunctional CaM kinase to mediate regulation of many cellular functions [8].
• The initial P/Q-type calcium signal is amplified by release of calcium from intracellular stores and acts through phosphorylation that is dependent on the calmodulin-dependent kinase CaM K II/IV, protein kinase A and mitogen-activated protein kinase kinase [9].
• The cAMP kinase incorporates one mol phosphate per mol of the 142K peptide and binding of (+)PN-200/110, a potent Ca antagonist, is allosterically affected by D-cis-diltiazem and verapamil [10].
• Multifunctional calcium-calmodulin-dependent protein kinase (CaM kinase) transduces transient elevations in intracellular calcium into changes in the phosphorylation state and activity of target proteins [11].

Chemical compound and disease context of CAMK1D

• We investigated the effects of cocaine, in concentrations commonly found in chronic cocaine users, on calcium/calmodulin kinase (CaMK), and whether cocaine can activate CaMK, increase cardiac myocyte protein expression, and cause cardiac hypertrophy in this manner [12].
• The effects of immunosuppressants and inhibitors of specific calcium/calmodulin kinase (CaMK) of types II and IV on progestin/glucocorticosteroid-induced transcription were studied in two human stably transfected breast cancer T47D cell lines [13].

Biological context of CAMK1D

• CKLiK kinase activity was dependent on Ca(++) and calmodulin as analyzed by in vitro phosphorylation of cyclic adenosine monophosphate responsive element modulator (CREM) [14].
• Up-regulation of CKLiK mRNA occurs during neutrophilic differentiation of CD34(+) stem cells [14].
• Thus, our results indicate that Ca(2+) triggers cross-talk signal transduction between CaM kinase and NO and CaM-K IIalpha phosphorylating nNOS on Ser(847), which in turn decreases the gaseous second messenger NO in neuronal cells [15].
• We conclude that, in human mesangial cells, CaMK and PKA can both contribute to cell cycle entry, and, although induction of c-fos by CaMK requires active PKA, neither pathway antagonizes or synergizes c-fos induction by the other [16].
• Treatment of H295R cells with calcium/calmodulin-dependent protein kinase (CaMK) inhibitor (KN93) or calmodulin inhibitor (calmidazolium) blocked angiotensin II and potassium (K(+)) stimulation of CYP11B2 reporter gene expression [17].

Anatomical context of CAMK1D

• Characterization of the role of CaMKI-like kinase (CKLiK) in human granulocyte function [18].
• Analysis of CKLiK messenger RNA (mRNA) expression in hematopoietic cells demonstrated an almost exclusive expression in human polymorphonuclear leukocytes (PMN) [14].
• In vivo activation of CKLiK was shown by addition of interleukin (IL)-8 to a myeloid cell line stably expressing CKLiK [14].
• Using a novel antibody generated against the C-terminus of CKLiK, CKLiK was detected in CD34+-derived neutrophils and eosinophils, as well as in mature peripheral blood granulocytes [18].
• Here we show that the sites of phosphorylation by four kinases (PKA, PKC, CK and CaMK) all lie in the C-terminal microtubule-binding half of tau, but only the phosphorylation by CaM kinase shows the pronounced shift in electrophoretic mobility characteristic for tau from Alzheimer neurofibrillary tangles [19].

Associations of CAMK1D with chemical compounds

• These data indicate a role for CaM kinase stimulation and resultant threonine phosphorylation of NMHC-IIA in RBL-2H3 m1 cell activation [20].
• CaMK but not PKA signaling is suppressed by low concentrations of heparin [16].
• Selective stimulation of CaMK with Ca(2+) ionophores and of PKA with forskolin or dibutyryl cAMP both result in induction of c-fos mRNA [16].
• In series V and VI, cocaine effects on calcium currents (ICa) and intracellular Ca ([Ca]i) were determined before and after CaMK inhibition with KN-62 in rat myocytes [12].
• Whereas CaMK inhibition affected neither integrin-stimulated Akt phosphorylation nor p21Ras or Mek-1 activity, it was necessary for Raf-1 activity [21].

Other interactions of CAMK1D

• They also exhibit a distinct ability to undergo autophosphorylation and to phosphorylate the downstream kinases CaMK I and CaMK IV [22].
• To determine which multifunctional CaMK acts in G(1), we expressed kinase-deficient forms of CaMKI and CaMKII [23].
• Supporting this finding, CaM-K inhibition using KN-93 also resulted in a reduction of cyclin D1 protein and pRb phosphorylation when cells were compared with control cultures [24].
• The calmodulin-dependent kinase (CaM-K) cascade, a Ca2+-triggered system involving phosphorylation and activation of CaM-KI and CaM-KIV by CaM kinase kinase (CaM-KK), regulates transcription through direct phosphorylation of transcription factors such as cAMP response element-binding protein [25].
• The inhibitory effect of CaM-K II on IL-2 promoter was associated with decreased transcription of its AP-1 and NF-AT transactivating pathways [26].

Analytical, diagnostic and therapeutic context of CAMK1D

• Molecular cloning and characterization of CLICK-III/CaMKIgamma, a novel membrane-anchored neuronal Ca2+/calmodulin-dependent protein kinase (CaMK) [27].
• Novel (Rp)-cAMPS analogs as tools for inhibition of cAMP-kinase in cell culture. Basal cAMP-kinase activity modulates interleukin-1 beta action [28].
• In series I to III, 0 (control) or cocaine in concentrations of 10 to 10 mol/L was added to cultured adult rat cardiac ventricular myocytes to determine by Western blots and by P incorporation the optimal treatment time and the optimal dose for CaMK activation [12].
• In series IV we measured by silver staining beta-myosin heavy chain protein (beta-MHC) expression in myocytes before and after cocaine and also CaMK inhibition with KN-62 (1-[N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine) [12].
• Gel band shift assays and densitometry experiments with intact CaM kinase I and the CaM-binding domain peptide (CaMKIp) reveal that they bind in an analogous manner, giving rise to 1:1 complexes [29].

References