共查询到20条相似文献,搜索用时 125 毫秒
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Protein kinase C (PKC) is an important signaling molecule in the heart, but its targets remain unclear. Using a PKC substrate
antibody, we detected a 40-kDa phosphorylated cardiac protein that was subsequently identified by tandem mass spectroscopy
as muscle creatine kinase (M-CK) with phosphorylation at serine 128. The forward reaction using ATP to generate phosphocreatine
was reduced, while the reverse reaction using phosphocreatine to generate ATP was increased following dephosphorylation of
immunoprecipitated M-CK with protein phosphatase 2A (PP2A) or PP2C. Despite higher PKC levels in diabetic hearts, decreased
phosphorylation of M-CK was more prominent than the reduction in its expression. Changes in CK activity in diabetic hearts
were similar to those found following dephosphorylation of M-CK from control hearts. The decrease in phosphorylation may act
as a compensatory mechanism to maintain CK activity at an appropriate level for cytosolic ATP regeneration in the diabetic
heart.
Received 15 September 2008; received after revision 30 September 2008; accepted 13 October 2008 相似文献
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Thomas Iskratsch Susan Reijntjes Joseph Dwyer Paul Toselli Irene R. Dégano Isabel Dominguez Elisabeth Ehler 《Cellular and molecular life sciences : CMLS》2013,70(5):893-908
Posttranslational modifications such as phosphorylation are universally acknowledged regulators of protein function. Recently we characterised a striated muscle-specific isoform of the formin FHOD3 that displays distinct subcellular targeting and protein half-life compared to its non-muscle counterpart and which is dependent on phosphorylation by CK2 (formerly casein kinase 2). We now show that the two isoforms of FHOD3 are already expressed in the vertebrate embryonic heart. Analysis of CK2 alpha knockout mice showed that phosphorylation by CK2 is also required for proper targeting of muscle FHOD3 to the myofibrils in embryonic cardiomyocytes in situ. The localisation of muscle FHOD3 in the sarcomere varies depending on the maturation state, being either broader or restricted to the Z-disc proper in the adult heart. Following myofibril disassembly, such as that in dedifferentiating adult rat cardiomyocytes in culture, the expression of non-muscle FHOD3 is up-regulated, which is reversed once the myofibrils are reassembled. The shift in expression levels of different isoforms is accompanied by an increased co-localisation with p62, which is involved in autophagy, and affects the half-life of FHOD3. Phosphorylation of three amino acids in the C-terminus of FHOD3 by ROCK1 is sufficient for activation, which results in increased actin filament synthesis in cardiomyocytes and also a broader localisation pattern of FHOD3 in the myofibrils. ROCK1 can directly phosphorylate FHOD3, and FHOD3 seems to be the downstream mediator of the exaggerated actin filament formation phenotype that is induced in cardiomyocytes upon the overexpression of constitutively active ROCK1. We conclude that the expression of the muscle FHOD3 isoform is characteristic of the healthy mature heart and that two distinct phosphorylation events are crucial to regulate the activity of this isoform in thin filament assembly and maintenance. 相似文献
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Marchetta M Gamberi T Sarno S Magherini F Raugei G Camici G Pinna LA Modesti A 《Cellular and molecular life sciences : CMLS》2004,61(10):1176-1184
Although the yeast genome does not encode bona fide protein tyrosine kinases, tyrosine-phosphorylated proteins are numerous, suggesting that besides dual-specificity kinases, some Ser/Thr kinases are also committed to tyrosine phosphorylation in Saccharomyces cerevisiae. Here we show that blockage of the highly pleiotropic Ser/Thr kinase CK2 with a specific inhibitor synergizes with the overexpression of Stp1 low-molecular-weight protein tyrosine phosphatase (PTP) in inducing a severe growth-defective phenotype, consistent with a prominent role for CK2 in tyrosine phosphorylation in yeast. We also present in vivo evidence that immunophilin Fpr3, the only tyrosine-phosphorylated CK2 substrate recognized so far, interacts with and is dephosphorylated by Spt1. These data disclose a functional correlation between CK2 and LMW-PTPs, and suggest that reversible phosphorylation of Fpr3 plays a role in the regulation of growth rate and budding in S. cerevisiae.Received 15 January 2004; received after revision 20 February 2004; accepted 4 March 2004 相似文献
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A. Venerando L. Cesaro O. Marin A. Donella-Deana L. A. Pinna 《Cellular and molecular life sciences : CMLS》2014,71(12):2193-2196
The motif “SYDE”, incorporating the protein kinase CK2 consensus sequence (S-x-x-E) has been found to be phosphorylated at both its serine and tyrosine residues in several proteins. Of special interest is the case of cystic fibrosis Transmembrane-conductance Regulator (CFTR), where this motif is close to the residue (F508), whose deletion is the by far commonest cause of cystic fibrosis. Intriguingly, however, CFTR S511 cannot be phosphorylated by CK2 to any appreciable extent. Using a number of peptide substrates encompassing the CFTR “SYDE” site we have recently shown that: (1) failure of CK2 to phosphorylate the S511YDE motif is due to the presence of Y512; (2) CK2 readily phosphorylates S511 if Y512 is replaced by a phospho-tyrosine; (3) the Src family protein tyrosine kinase Lyn phosphorylates Y512 in a manner that is enhanced by the deletion of F508. These data, in conjunction with the recent observation that by inhibiting CK2 the degradation of F508delCFTR is reduced, lead us to hypothesize that the hierarchical phosphorylation of the motif SYDE by the concerted action of protein tyrosine kinases and CK2 is one of the mechanisms that cooperate to the premature degradation of F508delCFTR. 相似文献
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G Bailin 《Experientia》1984,40(11):1185-1188
In smooth muscle the Mr 20,000 light chain of myosin is phosphorylated by a calmodulin-dependent protein kinase. It consists of 2 subunits: calmodulin, an acidic protein of Mr 17,000 that binds 4 moles of Ca2+; and a larger protein of Mr circa 130,000. Activation of the kinase is dependent upon their association in the presence of Ca2+. Cyclic AMP-dependent protein kinase phosphorylation of the myosin light chain kinase occurs at 2 sites. It decreases the affinity of the kinase for calmodulin and a reduction in the rate of light chain phosphorylation occurs. The kinase has an overall asymmetric shape composed of a globular head and tail region for the skeletal muscle enzyme. Trypsin digestion of this kinase releases a fragment of Mr 36,000 from the globular region that contains the catalytic and calmodulin binding sites. Chymotrypsin digestion of the kinase from smooth muscle generates a fragment of Mr 80,000 that does not contain the calmodulin binding or cyclic AMP-dependent protein kinase phosphorylation sites. It is a Ca2+-independent form of the kinase that phosphorylates the light chain of myosin. These structural features indicate a regulatory role for the kinase in smooth muscle phosphorylation and contraction. 相似文献
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Higgins JM 《Cellular and molecular life sciences : CMLS》2003,60(3):446-462
The haspins constitute a newly defined protein family containing a distinctive C-terminal eukaryotic protein kinase domain and divergent N termini. Haspin homologues are found in animals, plants and fungi, suggesting an origin early in eukaryotic evolution. Most species have a single haspin homologue. However, Saccharomyces cerevisiae has two such genes, while Caenorhabditis elegans has at least three haspin homologues and approximately 16 haspin-related genes. Mammalian haspin genes have features of retrogenes and are strongly expressed in male germ cells and at lower levels in some somatic tissues. They encode nuclear proteins with serine/threonine kinase activity. Murine haspin is reported to inhibit cell cycle progression in cell lines. One of the S. cerevisiae homologues, ALK1, is a member of the CLB2 gene cluster that peaks in expression at M phase and thus may function in mitosis. Therefore, the haspins are an intriguing group of kinases likely to have important roles during or following both meiosis and mitosis. 相似文献
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Andrea Venerando Oriano Marin Giorgio Cozza Victor H. Bustos Stefania Sarno Lorenzo Alberto Pinna 《Cellular and molecular life sciences : CMLS》2010,67(7):1105-1118
The ability of three isoforms of protein kinase CK1 (α, γ1, and δ) to phosphorylate the N-terminal region of p53 has been assessed using either recombinant p53 or a synthetic peptide
reproducing its 1–28 sequence. Both substrates are readily phosphoylated by CK1δ and CK1α, but not by the γ isoform. Affinity
of full size p53 for CK1 is 3 orders of magnitude higher than that of its N-terminal peptide (K
m 0.82 μM vs 1.51 mM). The preferred target is S20, whose phosphorylation critically relies on E17, while S6 is unaffected
despite displaying the same consensus (E-x-x-S). Our data support the concept that non-primed phosphorylation of p53 by CK1
is an isoform-specific reaction preferentially affecting S20 by a mechanism which is grounded both on a local consensus and
on a remote docking site mapped to the K221RQK224 loop according to modeling and mutational analysis. 相似文献
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Giovanni Di Maira Francesca Brustolon Lorenzo A. Pinna Maria Ruzzene 《Cellular and molecular life sciences : CMLS》2009,66(20):3363-3373
Akt (PKB) is a critical kinase in cell-survival pathways. Its activity depends on the phosphorylation of Thr308 and Ser473,
by PDK1 and mTORC2, respectively. We found that Akt can be further stimulated through phosphorylation of Ser129 by another
kinase, CK2. Here we show that phosphorylation of Akt at Ser129 also facilitates its association with Hsp90 chaperone, thus
preventing Thr308 dephosphorylation. This is supported by the following observations: (1) phospho-Thr308 decreases when Ser129
is mutated to alanine, (2) this decrease is abolished by cell treatment with okadaic acid (to inactivate PP2A) or geldanamycin
(to inactivate Hsp90), (3) phosphorylation of Ser129 neither enhances the activity of PDK1 nor hampers the in vitro activity
of PP2A on Thr308, but increases the Hsp90 association to Akt. These data support the view that the antiapoptotic potential
of CK2 is at least in part mediated by its ability to maintain Akt in its active form. 相似文献
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Dong Gao Ruipeng Wang Bingfeng Li Yongkang Yang Zhonghe Zhai Dan-Ying Chen 《Cellular and molecular life sciences : CMLS》2009,66(15):2573-2584
Toll-like receptors (TLRs) act as sensors of microbial components and elicit innate immune responses. All TLR signaling pathways
activate the nuclear factor-kappaB (NF-κB), which controls the expression of inflammatory cytokine genes. Transforming growth
factor-β-activated kinase 1 (TAK1) is a serine/threonine protein kinase that is critically involved in the activation of NF-κB
by tumor necrosis factor (TNFα), interleukin-1β (IL-1β) and TLR ligands. In this study, we identified a novel protein, WD40
domain repeat protein 34 (WDR34) as a TAK1-interacting protein in yeast two-hybrid screens. WDR34 interacted with TAK1, TAK1-binding
protein 2 (TAB2), TAK1-binding protein 3 (TAB3) and tumor necrosis factor receptor-associated factor 6 (TRAF6) in overexpression
and under physiological conditions. Overexpression of WDR34 inhibited IL-1β-, polyI:C- and lipopolysaccharide (LPS)-induced
but not TNFα-induced NF-κB activation, whereas knockdown of WDR34 by a RNA-interference construct potentiated NF-κB activation
by these ligands. Our findings suggest that WDR34 is a TAK1-associated inhibitor of the IL-1R/TLR3/TLR4-induced NF-κB activation
pathway.
D. Gao and R. Wang contributed equally to this work. 相似文献
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G. Bailin 《Cellular and molecular life sciences : CMLS》1984,40(11):1185-1188
Summary In smooth muscle the Mr 20,000 light chain of myosin is phosphorylated by a calmodulin-dependent protein kinase. It consists of 2 subunits: calmodulin, an acidic protein of Mr 17,000 that binds 4 moles of Ca2+; and a larger protein of Mr circa 130,000. Activation of the kinase is dependent upon their association in the presence of Ca2+. Cyclic AMP-dependent protein kinase phosphorylation of the myosin light chain kinase occurs at 2 sites. It decreases the affinity of the kinase for calmodulin and a reduction in the rate of light chain phosphorylation occurs. The kinase has an overall asymmetric shape composed of a globular head and tail region for the skeletal muscle enzyme. Trypsin digestion of this kinase releases a fragment of Mr 36,000 from the globular region that contains the catalytic and calmodulin binding sites. Chymotrypsin digestion of the kinase from smooth muscle generates a fragment of Mr 80,000 that does not contain the calmodulin binding or cyclic AMP-dependent protein kinase phosphorylation sites. It is a Ca2+-independent form of the kinase that phosphorylates the light chain of myosin. These structural features indicate a regulatory role for the kinase in smooth muscle phosphorylation and contraction. 相似文献
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Lan Shen Xuewu Liu Wugang Hou Guodong Yang Yousheng Wu Rui Zhang Xia Li Honglei Che Zifan Lu Yuanqiang Zhang Xinping Liu Libo Yao 《Cellular and molecular life sciences : CMLS》2010,67(8):1371-1381
The N-myc downstream-regulated gene 2 (NDRG2) is involved in cell differentiation and apoptosis, but its function in the pancreas remains to be established. Herein we examine the expression and function of NDRG2 in the endocrine pancreas. NDRG2 immunoreactivity was localized mainly in the cytoplasm of pancreatic β cells. When β-TC3 cells were exposed chronically to high levels of free fatty acid (FFA), cell viability was impaired, and Akt and NDRG2 phosphorylation were reduced. NDRG2 is a potential substrate of protein kinase Akt. Overexpression of constitutively active Akt enhanced NDRG2 phosphorylation and abolished the apoptosis induced by FFA in β-TC3 cells, whereas NDRG2 knock-down attenuated Akt-mediated protection of β cells against fatty acid-triggered apoptosis. Collectively, these data indicate that NDRG2 acts as a key molecule in pancreatic β cells and is involved in the Akt-mediated protection of β cells against lipotoxicity. 相似文献
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Polyamine-dependent gene expression 总被引:15,自引:0,他引:15
The polyamines spermidine and spermine along with the diamine putrescine are involved in
many cellular processes, including chromatin condensation, maintenance of DNA structure, RNA
processing, translation and protein activation. The polyamines influence the
formation of compacted chromatin and have a well-established role in DNA aggregation. Polyamines
are used in the posttranslational modification of eukaryotic initiation factor 5A, which regulates
the transport and processing of specific RNA. The polyamines also participate in a
novel RNA-decoding mechanism, a translational frameshift, of at least two known genes, the TY1
transposon and mammalian antizyme. Polyamines are crucial for their own regulation and are involved
in feedback mechanisms affecting both polyamine synthesis and catabolism. Recently, it has become
apparent that the polyamines are able to influence the action of the protein kinase
casein kinase 2. Here we address several roles of polyamines in gene expression.Received 27 November 2002; received after revision 9 January 2003; accepted 31 January 2003 相似文献
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Nadja Mannowetz Sabine Kartarius Gunther Wennemuth Mathias Montenarh 《Cellular and molecular life sciences : CMLS》2010,67(22):3905-3913
Protein kinase CK2 is an ubiquitously expressed enzyme that is absolutely necessary for the survival of cells. Besides the
holoenzyme consisting of the regulatory β-subunit and the catalytic α- or α′-subunit, the subunits exist in separate forms.
The subunits bind to a number of other cellular proteins. We show the expression of individual subunits as well as interaction
with the transitional nuclear protein TNP1 and with the motor neuron protein KIF5C during spermatogenesis. TNP1 is a newly
identified binding partner of the α-subunit of CK2. CK2α and KIF5C were found in late spermatogenesis, whereas CK2β and TNP1
were found in early spermatogenesis. CK2α, CK2α′, TNP1, and KIF5C were detected in the acrosome of spermatozoa, while CK2β
was detectable in the mid-piece. Combinations of CK2 subunits might determine interactions with other proteins during spermatogenesis.
KIF5C as a kinesin motor neuron protein is probably involved in the redistribution of proteins during spermatogenesis. 相似文献
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Regulation of transcription factor function by phosphorylation 总被引:1,自引:1,他引:0