Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have analyzed the in vitro phosphorylation of tau protein by Ca2+/calmodulin-dependent protein kinase, casein kinase II, and proline-directed serine/threonine protein kinase. These kinases phosphorylate tau protein in sites localized in different regions of the molecule, as determined by peptide mapping analyses. Focusing on the phosphorylation of tau by protein kinase C, it was calculated as an incorporation of 4 mol of phosphate/mol of tau. Limited proteolysis assays suggest that the phosphorylation sites could be located within the tubulin-binding domain. Direct phosphorylation of synthetic peptides corresponding to the cysteine-containing tubulin-binding region present in both fetal and adult tau isoforms demonstrates that serine 313 is modified by protein kinase C. Phosphorylation of the synthetic peptide by protein kinase C diminishes its binding to tubulin, as compared with the unphosphorylated peptide.
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PMID:Microtubule-associated protein tau is phosphorylated by protein kinase C on its tubulin binding domain. 163 8

Southern blot analysis of Chinese hamster x mouse somatic cell hybrids was used to map the gene for a serine/threonine protein kinase expressed in brain and testis. This locus, termed Camk-4, encodes Ca2+/calmodulin-dependent protein kinase IV. Progeny of an interspecific backcross were analyzed to position Camk-4 in the centromeric region of chromosome 18 near two mutations known to affect neurological function and fertility. This raises the possibility that a defect in Camk-4 may be responsible for one of these mutant phenotypes.
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PMID:Genetic mapping of the gene for Ca2+/calmodulin-dependent protein kinase IV (Camk-4) to mouse chromosome 18. 198 Oct 56

The dominant insulin-stimulated ribosomal protein S6 kinase activity was purified to near homogeneity from insulin-treated 32P-labeled rat H4 hepatoma cells and found to copurify with a 70-kDa 32P-labeled polypeptide. The dominant S6 kinase purified from livers of cycloheximide-treated rats is also a 70-kDa polypeptide. Antiserum raised against rat liver S6 kinase specifically immunoprecipitates the purified 32P-labeled H4 hepatoma insulin-stimulated S6 kinase. This antiserum also specifically precipitates insulin-stimulated S6 kinase activity directly from cytosolic extracts of H4 cells. Immune complexes prepared from the cytosol of 32P-labeled H4 cells contain several 32P-labeled polypeptides; only a 70-kDA 32P-labeled peptide, however, is specifically displaced by preadsorption of the antiserum with nonradioactive rat liver S6 kinase. Insulin treatment increases the 32P content of the immunoprecipitated 70-kDa S6 kinase polypeptide 3- to 4-fold over basal levels; 32P-labeled serine, some 32P-labeled threonine, but no 32P-labeled tyrosine are detected after partial acid hydrolysis. Tryptic peptide maps indicate that the insulin-stimulated S6 kinase purified from 32P-labeled H4 cells is phosphorylated at multiple sites distinct from those which participate in autophosphorylation in vitro. Autophosphorylation of rat liver S6 kinase in vitro does not modify S6 kinase activity. The S6 kinases purified from liver of cycloheximide-treated rat and H4 hepatoma insulin-stimulated enzyme are each completely deactivated by incubation with protein phosphatase type 2A in both autophosphorylating and 40S S6 phosphorylating activities. The phosphatase 2A-deactivated 70-kDa S6 kinase is neither reactivated nor phosphorylated by partially purified insulin-stimulated microtubule-associated protein 2 kinase, in experiments where Xenopus S6 kinase II undergoes phosphorylation and partial reactivation. Thus insulin activates the 70-kDa S6 kinase by promoting phosphorylation of specific serine/threonine residues on the enzyme polypeptide, probably through activating an as-yet-unidentified serine/threonine protein kinase distinct from microtubule-associated protein 2 kinase.
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PMID:Insulin activates a 70-kDa S6 kinase through serine/threonine-specific phosphorylation of the enzyme polypeptide. 212 50

Three different types of experiments are presented in this paper, the results of which converge to indicate that the viral src protein associates with and modulates the activity and/or the specificity of a serine/threonine protein kinase. Firstly, a 60-kDa protein from extracts of FR3T3 rat fibroblasts transformed by wild-type Rous sarcoma virus (SRD-FR3T3) is shown to be immunoprecipitated with a monoclonal antibody (mAb) raised against bacterially produced pp60v-src, the mAb327 [Lipsich, L. A., Lewis, A. J. & Brugge, J. S. (1983) J. Virol. 48, 352-360] and to be phosphorylated in vitro at serine/threonine/tyrosine residues, in the ratio 25:53:22. Under the same experimental conditions, the pp60c-src protein immunoprecipitated with mAb327 from extracts of NIH c-src overexpresser cells is phosphorylated exclusively on tyrosine residues. Secondly, the results of immunoprecipitation experiments using a tumor-bearing rabbit (TBR) serum and reported in an earlier work [David-Pfeuty, T. & Hovanessian, A. (1984) Eur. J. Biochem. 140, 325-342], together with those reported here, suggest that the TBR-immunoprecipitated pp60v-src coprecipitates with a cellular protein related to the 60-kDa subunit of the Ca2+/calmodulin protein kinase II from brain. Finally, partially purified preparations of pp60v-src, but not of pp60c-src, are shown to contain a Ca2+/calmodulin-dependent protein kinase activity that phosphorylates a 52-kDa protein substrate.
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PMID:Serine/threonine-specific protein kinase activity associated with viral pp60src protein. 216 17

Ca2+/calmodulin-dependent protein kinase II (CaMK II) is a multifunctional serine/threonine protein kinase that regulates ion channels, metabolic enzymes, cytoskeletal proteins, and possibly transcription factors. CaMK II holoenzymes have been shown to be large oligomers built from eight or more subunits. The oligomeric structure of CaMK II is required for a critical trans-autophosphorylation step by which each subunit traps bound calmodulin and renders the enzyme partially active in the absence of Ca2+/calmodulin. Here we define a minimal C-terminal domain of alphaCaMK II that is necessary and sufficient for oligomerization. The oligomeric structure of alphaCaMK II deletion mutants was investigated in vitro by gel filtration chromatography and in living cells by measuring nuclear exclusion and diffusion coefficients of green fluorescent protein-tagged mutants. These studies showed that a C-terminal region of alphaCaMK II of 135 amino acids is sufficient for oligomer formation. Oligomer formation was abolished by further C-terminal and N-terminal deletions, indicating that the same region is not only sufficient but also necessary for oligomerization. Thus, an oligomerization domain of only 15 kDa is sufficient to build the circular structure of CaMK II holoenzyme.
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PMID:In vivo and in vitro characterization of the sequence requirement for oligomer formation of Ca2+/calmodulin-dependent protein kinase IIalpha. 942 51

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine protein kinase that regulates long-term potentiation and other forms of neuronal plasticity. Functional differences between the neuronal CaMKIIalpha and CaMKIIbeta isoforms are not yet known. Here, we use green fluorescent protein-tagged (GFP-tagged) CaMKII isoforms and show that CaMKIIbeta is bound to F-actin in dendritic spines and cell cortex while CaMKIIalpha is largely a cytosolic enzyme. When expressed together, the two isoforms form large heterooligomers, and a small fraction of CaMKIIbeta is sufficient to dock the predominant CaMKIIalpha to the actin cytoskeleton. Thus, CaMKIIbeta functions as a targeting module that localizes a much larger number of CaMKIIalpha isozymes to synaptic and cytoskeletal sites of action.
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PMID:CaMKIIbeta functions as an F-actin targeting module that localizes CaMKIIalpha/beta heterooligomers to dendritic spines. 976 45

Ca2+/calmodulin-dependent protein kinase IV (Camk4; also known as CaMKIV), a multifunctional serine/threonine protein kinase with limited tissue distribution, has been implicated in transcriptional regulation in lymphocytes, neurons and male germ cells. In the mouse testis, however, Camk4 is expressed in spermatids and associated with chromatin and nuclear matrix. Elongating spermatids are not transcriptionally active, raising the possibility that Camk4 has a novel function in male germ cells. To investigate the role of Camk4 in spermatogenesis, we have generated mice with a targeted deletion of the gene Camk4. Male Camk4-/- mice are infertile with impairment of spermiogenesis in late elongating spermatids. The sequential deposition of sperm basic nuclear proteins on chromatin is disrupted, with a specific loss of protamine-2 and prolonged retention of transition protein-2 (Tnp2) in step-15 spermatids. Protamine-2 is phosphorylated by Camk4 in vitro, implicating a connection between Camk4 signalling and the exchange of basic nuclear proteins in mammalian male germ cells. Defects in protamine-2 have been identified in sperm of infertile men, suggesting that our results may have clinical implications for the understanding of human male infertility.
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PMID:Spermiogenesis and exchange of basic nuclear proteins are impaired in male germ cells lacking Camk4. 1093 93

Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) is a serine/threonine protein kinase with limited tissue distribution. CaMKIV is highly expressed in the testis, where it is found in transcriptionally inactive elongating spermatids. We have recently generated mice deficient in CaMKIV. In the absence of CaMKIV, the exchange of sperm nuclear basic proteins in male spermatids is impaired, resulting in male infertility secondary to defective spermiogenesis. The involvement of CaMKIV in female fertility has not been addressed. Here we report that female fertility is markedly reduced in CaMKIV-deficient mice due to impaired follicular development and ovulation. CaMKIV is expressed in the ovary, where it is localized in granulosa cells. We further find that in cultured granulosa cells, CaMKIV expression and subcellular localization are hormonally regulated. As granulosa cells differentiate, CaMKIV levels decrease and the kinase translocates from the nucleus into the cytoplasm. Our results demonstrate a critical role for CaMKIV in female reproduction and point to a potential function in granulosa cell differentiation.
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PMID:Female fertility is reduced in mice lacking Ca2+/calmodulin-dependent protein kinase IV. 1110 93

The AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine protein kinase important for the responses to metabolic stress. It consists of a catalytic alpha subunit and two non-catalytic subunits, beta and gamma, and is regulated both by the allosteric action of AMP and by phosphorylation of the alpha and beta subunits catalyzed by AMPKK(s) and autophosphorylation. The Thr172 site on the alpha subunit has been previously characterized as an activating phosphorylation site. Using bacterially expressed AMPK alpha1 subunit proteins, we have explored the role of Thr172-directed AMPKKs in alpha subunit regulation. Recombinant alpha1 subunit proteins, representing the N-terminus, have been expressed as maltose binding protein (MBP) 6x His fusion proteins and purified to homogeneity by Ni(2+) chromatography. Both wild-type alpha1(1-312) and alpha1(1-312)T172D are inactive when expressed in bacteria, but the former can be fully phosphorylated (1 mol/mol) on Thr172 and activated by a surrogate AMPKK, CaMKKbeta. The corresponding AMPKalpha1(1-392), an alpha construct containing its autoinhibitory sequence, can be similarly phosphorylated, but it remains inactive. In an insulinoma cell line, either low glucose or 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) treatment leads to activation and T172 phosphorylation of endogenous AMPK. Under the same conditions of cell incubation, we have identified an AMPKK activity that both phosphorylates and activates the recombinant alpha1(1-312), but this Thr172-directed AMPKK activity is unaltered by low glucose or AICAR, indicating that it is constitutively active.
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PMID:AMP-activated protein kinase kinase: detection with recombinant AMPK alpha1 subunit. 1205 42

The serine/threonine protein kinase B (PKB)/Akt is a phosphoinositide 3-kinase (PI3K) effector that is thought to play an important roll in a wide variety of cellular events. The present study examined whether PKB activation in cortical neuronal cultures is coupled with synaptic activity. A 1-h incubation of neuronal cultures with tetrodotoxin (TTX), the PI3K inhibitor wortmannin, the NMDA receptor antagonist MK-801 or removal of extracellular calcium significantly reduced basal levels of phospho(Ser473)-PKB, indicating that activity-dependent glutamate release maintains PKB activation through an NMDA receptor-PI3K pathway. A 5-min exposure to NMDA (50 micro m) in the presence of TTX increased phospho-PKB back to levels observed in the absence of TTX. NMDA stimulation of phospho-PKB was blocked by wortmannin, the CaMKII inhibitor KN-93, MK-801, and removal of extracellular calcium. We have previously shown that NMDA receptors can bi-directionally regulate activation of extracellular-signal regulated kinase (ERK), and NMDA receptor stimulation of PKB in the present study appeared to mirror activation of ERK. These results suggest that in cultured cortical neurons, PKB activity is dynamically regulated by synaptic activity and is coupled to NMDA receptor activation. In addition, NMDA receptor activation of ERK and PKB may occur through overlapping signaling pathways that bifurcate at the level of Ras.
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PMID:Activity-dependent NMDA receptor-mediated activation of protein kinase B/Akt in cortical neuronal cultures. 1235 57


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