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

The activity of eukaryotic elongation factor 2 is regulated by phosphorylation catalysed by a highly specific Ca2+/calmodulin-dependent protein kinase. Phosphorylated EF2 binds to ribosomes with decreased affinity. The present evidence indicates that EF2 prebound to ribosomes is protected from phosphorylation, just as earlier evidence indicated that ribosome-bound EF2 is protected from ADP-ribosylation catalysed by diphtheria toxin. Ribosome-inactivating proteins ricin and gelonin, by interfering with the EF2-ribosome interaction, allow full phosphorylation of EF2.
 ...
PMID:Ribosome-bound elongation factor 2 escapes phosphorylation by Ca2+/calmodulin-dependent protein kinase III. 132 54

Mammalian cells contain a Ca2+/calmodulin-dependent protein kinase that specifically phosphorylates and inactivates elongation factor 2 (EF-2) in response to hormones and other agents which increase intracellular Ca2+ concentrations. Therefore, it has been proposed that the rate of translation in mammals is regulated by EF-2 phosphorylation. In the present study, EF-2 purified from the yeast Saccharomyces cerevisiae is shown to be a substrate for the mammalian EF-2 kinase. Furthermore, evidence was obtained using two-dimensional gel electrophoresis and peptide mapping which suggests that yeast EF-2 is a substrate for an endogenous kinase which phosphorylates the same site as the mammalian EF-2 kinase. Based on these findings, we propose that in yeast as in higher eukaryotes, the protein synthesis elongation cycle is regulated by phosphorylation of EF-2.
 ...
PMID:Saccharomyces cerevisiae elongation factor 2 is phosphorylated by an endogenous kinase. 193 78

Calcium, adenosine 3',5'-cyclic monophosphate (cAMP), and guanosine 3',5'-cyclic monophosphate (cGMP) can regulate the same or different ion transport processes within an epithelium, presumably via independent protein phosphorylation mechanisms. Because there have been few detailed studies characterizing these processes in epithelia, we examined the distribution of Ca-, cAMP-, and cGMP-specific protein kinases and substrates in vitro in a homogenous salt-absorbing epithelium, the winter flounder intestine. In this tissue cGMP and Ca inhibit Na-K-2Cl cotransport, cAMP increases anion permeability, and phorbol esters do not affect ion transport. The Ca-specific kinases are calmodulin (CaM) dependent. The tissue possesses type III Ca-CaM protein kinase and its specific substrate elongation factor 2 and type II but not type I Ca-CaM kinase. Addition of phosphatidylserine (PS) and Ca to crude or DEAE-cellulose-purified cytosol neither increased the phosphorylation of exogenous histone H1 substrate nor that of any endogenous substrates. Although these suggest the absence of Ca-phospholipid-dependent kinase (PKC), the cytosol has a 78-kDa protein recognizable by a highly specific polyclonal sheep antibody to rat brain PKC. Both the particulate and cytosolic fractions possess cAMP-specific binding proteins and cAMP-specific phosphoprotein substrates. The particulate fraction cAMP-binding proteins are of molecular mass 50 kDa (pI 5.2) and 48 kDa with multiple isoforms (pI 5.6-6.2); these proteins generate different peptide maps. The cytosol chiefly contains a 50-kDa (pI 5.2) cAMP binding protein that is similar to the particulate 50-kDa protein on peptide mapping. The flounder cAMP binding proteins have the same pI but lower molecular mass and different peptide profiles than the rat brain RII (54/52 kDa) and RI (50 kDa) cAMP regulatory proteins. The cGMP-specific protein kinase was less prominent, very low levels of cGMP-specific binding proteins being detected either by equilibrium binding or by photoaffinity labeling. A prominent kinase substrate in homogenates is a 50-kDa protein, the phosphorylation of which is increased by Ca and cGMP but decreased by cAMP. When intact tissue was prelabeled with 32Pi and then exposed to cGMP, the phosphorylation of a number of substrates including that of a 50-kDa protein was increased. In summary, the flounder intestine possesses the necessary protein phosphorylation mechanisms to account for the regulation of its ion transport processes by second messengers.
 ...
PMID:Second messenger-specific protein kinases in a salt-absorbing intestinal epithelium. 215 31

Okadaic acid, a tumour promoter which potently inhibits protein phosphatases, inhibited translation in the reticulocyte-lysate cell-free system. Inhibition was dose-dependent, with half-maximal effects occurring at 20-40 nM-okadaic acid. Inhibition of translation by okadaic acid resulted in the accumulation of polyribosomes, indicating that it was due to a decrease in the rate of elongation relative to initiation. Okadaic acid (at concentrations which inhibited translation) caused increased phosphorylation of a number of proteins in the lysate. Prominent among these was a protein of Mr 100,000, which has previously been identified as elongation factor 2 (EF-2). EF-2 is a specific substrate for a Ca2+/calmodulin-dependent protein kinase, which phosphorylates EF-2 on threonine residues. The Mr-100,000 band was phosphorylated exclusively on threonine residues, and its degree of 32P labelling was decreased by the Ca2+ chelator EGTA and by the calmodulin antagonist trifluoperazine. These agents attenuated the effects of okadaic acid on EF-2 phosphorylation and translation. When ranges of concentrations of each agent were tested, their effects on EF-2 labelling correlated well with their ability to reverse the okadaic acid-induced inhibition of translation. These findings demonstrate that increased phosphorylation of EF-2 results in an impairment of peptide-chain elongation when natural mRNA is used. The possible physiological role of EF-2 phosphorylation in the control of translation is discussed.
 ...
PMID:The tumour promoter okadaic acid inhibits reticulocyte-lysate protein synthesis by increasing the net phosphorylation of elongation factor 2. 251 Jul 15

Previously we have found that elongation factor 2 (EF-2) from mammalian cells can be phosphorylated by a special Ca2+/calmodulin-dependent protein kinase (EF-2 kinase). Phosphorylation results in complete inactivation of EF-2 in the poly(U)-directed cell-free translation system. However, the partial function of EF-2 affected by phosphorylation remained unknown. Here we show that phosphorylated EF-2, unlike non-phosphorylated EF-2, is unable to switch ribosomes carrying poly(U) and Phe-tRNA in the A site to a puromycin-reactive state. Thus, phosphorylation of EF-2 seems to block its ability to promote a shift of the aminoacyl(peptidyl)-tRNA from the A site to the P site, i.e. translocation itself.
 ...
PMID:Mechanism of elongation factor 2 (EF-2) inactivation upon phosphorylation. Phosphorylated EF-2 is unable to catalyze translocation. 275 58

Sphingosine is a potent inhibitor of several calmodulin-dependent enzymes. The multifunctional Ca2+/calmodulin-dependent protein kinase, a Ca2+/calmodulin-dependent phosphodiesterase, and smooth muscle myosin light chain kinase are inhibited in vitro at concentrations previously shown to inhibit protein kinase C. Inhibition of each of the enzymes is competitive with calmodulin, suggesting that sphingosine may be a calmodulin antagonist. In the pituitary cell line GH3, sphingosine inhibits the phosphorylation of microtubule-associated protein 2 by the multifunctional Ca2+/calmodulin-dependent protein kinase and the phosphorylation of elongation factor 2 by Ca2+/calmodulin-dependent kinase III. These findings suggest that sphingosine, in blocking the effects of both the Ca2+.calmodulin complex and of diacylglycerol, may be a very effective inhibitor of both branches of the phosphatidylinositol signaling pathway. By extension, caution should be exercised in the use of sphingosine as a diagnostic test for the involvement of protein kinase C in biological processes.
 ...
PMID:Sphingosine inhibits calmodulin-dependent enzymes. 284 4

Elongation factor 2 (EF-2) and its associated kinase, Ca2+/calmodulin-dependent protein kinase III, have recently been identified as a major protein phosphorylation system in mammalian tissues. We have measured the phosphorylation of EF-2 in 32P-labeled superior cervical ganglia. Phosphorylation of EF-2 was increased by preganglionic stimulation or by treatment of the ganglion with dimethylphenylpiperazinium or veratridine. Increases in EF-2 phosphorylation presumably reflect the activation of Ca2+/calmodulin-dependent protein kinase III by nicotinic stimulation and depolarization. The phosphorylation of EF-2 may help to coordinate neuronal protein synthesis with neuronal activity.
 ...
PMID:Phosphorylation of elongation factor 2 in the rat superior cervical ganglion. 335 61

A new Ca2+/calmodulin-dependent protein kinase has been recently discovered in mammalian cells. The major substrate of this kinase, a protein of relative molecular mass (Mr) approximately equal to 100,000 (100K), has been identified as elongation factor 2 (EF-2), which participates in protein synthesis. The in vivo activity of the EF-2 kinase depends upon growth factors and other agents affecting the level of Ca2+ and cAMP. Its effect on EF-2 activity, however, remained obscure. This work shows that the phosphorylation of EF-2 by the EF-2 kinase results in a drastic inhibition of polyphenylalanine synthesis in poly(U)-directed translation. Phosphorylated EF-2 is completely inactive in translation and, moreover, inhibits the activity of non-phosphorylated EF-2. Dephosphorylation of EF-2 by phosphatase restores its activity. Hence, the phosphorylation of EF-2 directly affects the elongation stage of translation and thus represents a novel mechanism of translational control.
 ...
PMID:Phosphorylation of elongation factor 2 by EF-2 kinase affects rate of translation. 338 56

The mitogenic activity of several growth factors is mediated by calcium-dependent signal transduction. Calmodulin (CaM) binding proteins such as CaM-dependent protein kinases are important components of this pathway and may be altered in diseases characterized by abnormal cell growth. CaM kinase II is believed to regulate the phosphorylation of microtubular-associated proteins and control the initiation of DNA synthesis. Furthermore, drugs that inhibit CaM-mediated signal transduction also inhibit cellular proliferation and are cytotoxic to numerous malignant cell lines, including those established from malignant gliomas. Yet, little is known about CaM-dependent protein kinases in these tumors. Therefore, we have investigated the activity and distribution of CaM-dependent protein kinase II in normal and malignant glial tissues, a kinase believed to play a critical role in cell cycle regulation. C6 and 9L cells contained kinase activities that were activated by Ca2+/CaM and inhibited by trifluoperazine. Tissue extracts from these cell lines and from rat brain white matter phosphorylated exogenous synapsin I in a pattern consistent with the presence of CaM kinase II activity as determined by phosphopeptide mapping. CaM kinase II activity was confirmed using a specific peptide substrate and inhibitor. An unexpected finding was that glioma lines, but not rat brain white matter, also contained a CaM-dependent protein kinase detected by the phosphorylation of a M(r) 100,000 protein, subsequently identified as elongation factor 2, the only known substrate for CaM kinase III.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Calmodulin-dependent protein kinases in rat glioblastoma. 764 41

A 20.5 kb DNA fragment from the left arm of chromosome XI of Saccharomyces cerevisiae has been sequenced and analysed. Thirteen open reading frames (ORFs) for proteins longer than 100 amino acids were discovered. Among them, two are the known genes MRP49 and TPK3; two others encode proteins which show strong similarity with a yeast putative protein kinase and a yeast choline transport protein; one other shows weaker similarity with a yeast Ca2+/calmodulin-dependent protein kinase. Moreover, two putative proteins encoded by ORFs located in the sequenced fragment are closely similar to non-yeast proteins: the Caenorhabditis elegans elongation factor 2 and a glutamic acid-rich protein of Plasmodium falciparum.
 ...
PMID:Sequencing and analysis of a 20.5 kb DNA segment located on the left arm of yeast chromosome XI. 809 58


1 2 Next >>