Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transcript for the high-affinity Ca2+/calmodulin-binding protein calspermin is generated from the gene encoding Ca2+/calmodulin-dependent protein kinase IV only in postmeiotic germ cells during spermatogenesis. We demonstrate that this testis-specific calspermin transcript can be produced in heterologous cells by utilization of a promoter located in an intron of the calmodulin (CaM) kinase IV gene. Critical motifs within this promoter are two cyclic AMP response element (CRE)-like sequences located about -70 and -50 bp upstream of the transcriptional initiation site. Both CRE motifs are footprinted by the authentic testis-specific transcriptional activator CREM tau or by CREM tau present in adult testis nuclear extract. Whereas a 2.1-kb DNA fragment containing the calspermin promoter is inactive when transfected into NIH 3T3 cells, activity can be restored by cotransfection of CREM tau and protein kinase A or CaM kinase IV but not CaM kinase II alpha. Restoration of activity is greatly reduced by mutation of the two CRE motifs. Since CRE-like motifs have been identified in many genes uniquely expressed in postmeiotic germ cells, which contain abundant CREM tau protein, we suggest that CREM tau may function as one transcription factor responsible for the expression of postmeiotic germ cell-specific genes.
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PMID:Calspermin gene transcription is regulated by two cyclic AMP response elements contained in an alternative promoter in the calmodulin kinase IV gene. 779 65

Calmodulin-dependent protein kinase IV (CaM-kinase IV) kinase was recently discovered in the rat brain by its activity to activate the inactive recombinant CaM-kinase IV expressed in Escherichia coli [Okuno, S. and Fujisawa, H. (1993) J. Biochem. 114, 167-170]. In the present study, CaM-kinase IV kinase was purified approximately 2,000-fold from rat cerebral cortex by purification procedures including calmodulin affinity chromatography, and its properties were examined. The highly purified CaM-kinase IV kinase gave one major protein band corresponding to a molecular weight of about 66,000 upon SDS-PAGE. The purified CaM-kinase IV kinase phosphorylated and concomitantly activated CaM-kinase IV purified from rat brain as well as the recombinant kinase expressed in Escherichia coli in a Ca2+/calmodulin-dependent manner. The phosphorylation of CaM-kinase IV by CaM-kinase IV kinase occurred on only serine residue(s). Among a number of proteins, including several known to be phosphorylated by the various protein kinases tested, CaM-kinase IV was the best substrate for CaM-kinase IV kinase. Since syntide-2, a synthetic peptide known to be a good peptide substrate for calmodulin-dependent protein kinase II (CaM-kinase II), was a fairly good substrate for CaM-kinase IV kinase, some kinetic properties of CaM-kinase IV kinase were examined using syntide-2 as a substrate. The Km value for the peptide substrate in the presence of Ca2+/calmodulin was almost two orders of magnitude lower than that in its absence, although the Vmax value was almost the same in the presence and absence of Ca2+/calmodulin.
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PMID:Purification and characterization of Ca2+/calmodulin-dependent protein kinase IV kinase from rat brain. 788 70

gamma-Aminobutyric acid type A receptor subunits (GABAA) can be divided into five classes, alpha, beta, gamma, delta, and rho, based on sequence homology. We have used purified fusion proteins of the major intracellular domain of GABAA receptor subunits produced in Escherichia coli to examine the phosphorylation of these subunits by cGMP-dependent protein kinase (PKG) and multifunctional calcium/calmodulin-dependent protein kinase (CAM KII). Both PKG and CAM KII phosphorylated a purified beta 1 subunit fusion. Both of these kinases phosphorylated serine 409 within the beta 1 subunit; in addition, CAM KII also phosphorylated serine 384 as determined by site-specific mutagenesis. Fusion proteins of the major intracellular domains of the gamma 2S and gamma 2L subunits were produced. These proteins differ by 8 amino acids (LLRMFSFK). Both the gamma 2L and gamma 2S fusion proteins were excellent substrates of CAM KII. However, the gamma 2L fusion protein was phosphorylated to higher stoichiometry due to the phosphorylation of serine 343 within this 8-amino acid insertion. Both the gamma 2L and gamma 2S subunits were phosphorylated on common residues by CAM KII identified as serine 348 and threonine 350. These results identify specific sites of phosphorylation for CAM KII and PKG within GABAA receptor subunits, suggesting a role for these two kinases in modulating GABAA receptor function in vivo.
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PMID:Differential phosphorylation of intracellular domains of gamma-aminobutyric acid type A receptor subunits by calcium/calmodulin type 2-dependent protein kinase and cGMP-dependent protein kinase. 802 73

Calmodulin-dependent protein kinase IV (CaM-kinase IV) is a Ca(2+)-responsive multifunctional protein kinase which occurs abundantly in the brain and thymus. A human cDNA clone encoding CaM-kinase IV was isolated from a Jurkat cell cDNA library and its nucleotide sequence was determined. The cDNA sequence encoded a protein consisting of 473 amino acids with a molecular weight of 51,925. The nucleotide sequence for the coding region and the deduced amino acid sequence showed 81 and 80% identities with those of the rat enzyme, respectively. Western blot analysis, using a polyclonal antibody raised against the recombinant human CaM-kinase IV, which was expressed in Escherichia coli, revealed two bands corresponding in mobility to molecular weights of 60,000 and 61,000, respectively, in a Jurkat cell extract. The antibody also cross-reacted with both isoforms of CaM-kinase IV from rat cerebellum, the apparent molecular weights being 62,000 and 64,000, respectively.
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PMID:cDNA cloning and expression of human calmodulin-dependent protein kinase IV. 808 75

We have characterized Ca2+/calmodulin-dependent protein kinase IV (CaM kinase IV), expressed using the baculovirus/Sf9 cell system, to assess its potential role in Ca2+-dependent transcriptional regulation. CaM kinase IV was strongly inhibited in vitro by KN-62, a specific CaM kinase inhibitor which suppresses Ca2+-dependent transcription of several genes, so we tested whether CaM kinase IV could stimulate transcription. Co-transfection of COS-1 cells by cDNA for CaM kinase IV gave 3-fold stimulation of a reporter gene expression, whereas co-transfection with CaM kinase II gave no transcriptional stimulation. Since this transcriptional response was mediated by phosphorylation of cAMP responsive element-binding protein (CREB), we determined the kinetics and site specificities of CaM kinases IV and II for phosphorylating CREB in vitro. CaM kinases IV and II and cAMP kinase (protein kinase A) all had similar Km values for CREB (1-5 microns), but the Vmax of CaM kinase IV was 40-fold lower than those of CaM kinase II and protein kinase A. Although all three kinases phosphorylated Ser133 in CREB, CaM kinase II also gave equal phosphorylation of a second site which was not Ser98. The two CREB phosphorylation sites were separately 32P-labeled, and the abilities of protein phosphatases 1, 2A, and 2B (calcineurin) to dephosphorylate them were tested. Our results show that all three phosphatases could dephosphorylate both sites, and calcineurin was a stronger catalyst for dephosphorylating site 1 (Ser133) than for site 2. These results indicate that CaM kinase IV may be important in Ca2+-dependent transcriptional regulation through phosphorylation of Ser133 in CREB. The fact that CaM kinase II phosphorylates another site in addition to Ser133 in CREB raises the possibility that this second phosphorylation site may account for the suppressed phosphorylation site may account for the suppressed ability of CaM kinase II to enhance transcription through the CRE/CREB system. In addition multiple protein phosphatases, including calcineurin, may exert a modulatory effect on transcription depending on which site they dephosphorylate.
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PMID:Characterization of Ca2+/calmodulin-dependent protein kinase IV. Role in transcriptional regulation. 819 96

Calmodulin-dependent protein kinase IV (CaM-kinase IV) is a Ca(2+)-responsive multifunctional protein kinase which occurs abundantly in the brain. When cDNA for rat brain CaM-kinase IV was expressed in Escherichia coli, the enzyme was produced in a good yield, but it did not show significant activity. The inactive recombinant CaM-kinase IV was phosphorylated and became highly active on incubation with a rat brain extract in the presence of both Ca2+/calmodulin and ATP/Mg2+. The recombinant CaM-kinase IV-activating activity in brain was one to two orders of magnitude higher than that in the other tissues examined. These observations suggest that CaM-kinase IV may undergo a posttranslational modification, probably Ca2+/calmodulin-dependent phosphorylation by CaM-kinase IV kinase, before exhibiting activity in the central nervous system.
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PMID:Requirement of brain extract for the activity of brain calmodulin-dependent protein kinase IV expressed in Escherichia coli. 826 94

Calmodulin-dependent protein kinase IV from rat cerebral cortex undergoes autophosphorylation in response to Ca2+ and calmodulin, resulting in its marked enzymatic activation. Autophosphorylation occurred at several sites on CaM-kinase IV, depending upon the enzyme concentration. Among them, Ser437 was almost exclusively phosphorylated at enzyme concentrations lower than 10 micrograms/ml, and autophosphorylation at Ser437 was responsible for marked activation of the enzyme through decreases in the Km values for its substrates and an increase in the Vmax value. The Ca2+/calmodulin-independent activity of CaM-kinase IV was also markedly stimulated by autophosphorylation, but even after autophosphorylation it amounted only about 17% of the total enzyme activity detected in the presence of Ca2+/calmodulin.
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PMID:Autophosphorylation of calmodulin-dependent protein kinase IV from rat cerebral cortex. 834 Mar 52

Calmodulin-kinase II (CaM kinase) is a calcium/calmodulin-dependent protein kinase which is highly enriched in the nervous system and mediates many of calcium's actions. Regulation of CaM kinase activity plays an important role in modulating synaptic transmission, synaptic plasticity and in neuropathology. Primary regulation of CaM kinase occurs via changes in intracellular calcium concentrations. Increased calcium stimulates protein kinase activity and induces autophosphorylation. Autophosphorylation of CaM kinase at specific sites results in altered activity and responsiveness to subsequent changes in calcium concentrations. Intracellular translocation of CaM kinase also appears to result from autophosphorylation. These mechanisms of regulation play an important role in synaptic plasticity (e.g., Aplysia ganglia), status epilepticus and cerebral ischemia. Long-lasting alterations in the expression of CaM kinase have been demonstrated in the kindling model of epilepsy and in monocular deprivation and therefore modulation of gene expression, in addition to autophosphorylation and translocation, appears to be another important mechanism of regulating CaM kinase activity.
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PMID:Regulation of type-II calmodulin kinase: functional implications. 838 27

Two cDNA clones (ASK1 and ASK2) for plant protein kinases were cloned from Arabidopsis thaliana by screening cDNA libraries with a degenerate oligonucleotide probe that corresponds to a highly conserved motif among protein kinases. Sequence analysis shows that the clones contain open reading frames that encode 41.2 kDa (ASK1) and 40.1 kDa (ASK2) proteins, respectively. These coding regions contain all the conserved motifs of protein kinases. Structural analysis of the coding regions revealed that the two protein kinase genes share high sequence similarity to each other (76.6% identity). The catalytic domain located in the amino terminal region is most similar to the calcium/calmodulin-dependent protein kinase subfamily (47.2% to 54.2% similarity) and the SNF1 kinase subfamily (48.1% to 53.3% similarity). However, the carboxy terminal regions contain distinctive stretches of 21 (ASK1) and 19 (ASK2) acidic amino acids. These clones are the first report of protein kinases with such acidic amino acid regions. The transcripts of both genes are most abundant in leaf but are also expressed in other organs. The expression of the two genes is highly affected by light regime.
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PMID:Two putative protein kinases from Arabidopsis thaliana contain highly acidic domains. 839 17

The aim of this work was to study whether changes in fructose 2,6-bisphosphate concentration are correlated with variations of the glycolytic flux in the isolated working rat heart. Glycolysis was stimulated to different extents by increasing the concentration of glucose, increasing the workload, or by the addition of insulin. The glycolytic flux was measured by the rate of detritiation of [2-3H]- and [3-3H]glucose. Under all the conditions tested, an increase in fructose 2,6-bisphosphate content was observed. The glucose- or insulin-induced increase in fructose 2,6-bisphosphate content was related to an increase in the concentration of fructose 6-phosphate, the substrate of 6-phosphofructo-2-kinase. An increase in the workload correlated with a 50% decrease in the Km of 6-phosphofructo-2-kinase for fructose 6-phosphate. Similar changes in Km have been observed when purified heart 6-phosphofructo-2-kinase was phosphorylated in vitro by the cyclic AMP-dependent protein kinase or by the calcium/calmodulin-dependent protein kinase. Since the concentration of cyclic AMP was not affected by increasing the workload, it is possible that the change in Km of 6-phosphofructo-2-kinase, which was found in hearts submitted to a high load, resulted from phosphorylation by calcium/calmodulin protein kinase; other possibilities are not excluded. Anoxia decreased the external work developed by the heart, stimulated glycolysis and glycogenolysis, but did not increase fructose 2,6-bisphosphate.
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PMID:Role of fructose 2,6-bisphosphate in the control of heart glycolysis. 851 65


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