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)

Yeast regulatory factor PHO85, which is a cyclin-dependent kinase (DCK), participates in the regulation of the cell cycle and the expression of the acid phosphatase gene. Using PHO85 as target, we have cloned from the yeast two-hybrid genomic library a novel gene (PAP1) with product which can asscociate with the PHO85 protein. The PAP1 gene including the 5apo; and 3apo; flanking sequence was cloned and sequenced. It codes for a protein composed of 284 amino acids, which contains a cyclin conservative region (150-263 aa), and shares 63% similarity with the conservative region of PHO80. The N-terminal of the PAP1 protein abounds in PEST sequence, which is believed to be common to rapidly degraded proteins. Using the yeast two-hybrid system, we demonstrated that both the full-length PAP1 protein and the C-terminal (99-285 aa) can interact with PHO85. The coding sequence of the PAP1 gene was cloned and sequenced, then arranged under the control of the P(L) promoter, and expressed in E. coli BL21 (DE3) pLysS. After heat induction at 42 degrees, protein band of approximately 32 kD was observed in the SDS-PAGE, which fits the molecular size of the hypothetical PAP1 protein. The 10 N-terminal amino acids of the 32 kD protein agreed with the deduced PAP1 amino acid sequence. The protein was found as inclusion body in E. coli, and accounted for 50% of the precipitant after purification.
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PMID:Cloning and Expression of a Novel PHO85 Associated Protein PAP1 Gene of Saccharomyces cerevisiae. 1217 91

Post-translational glutamylation of tubulin plays an important role in regulating the interaction between microtubules and associated proteins, but so far the enzymes involved in this process have not been cloned from any cellular source. Using a modified purification scheme that employs a hydroxyapaptite chromatography as the final step we identified a 54 kDa band as the major polypeptide copurifying with tubulin polyglutamylation activity from the trypanosomatid Crithidia fasciculata. Based on peptide sequence information we have cloned the corresponding cDNA and identify Crithidia p54 as a novel member (termed CfNek) of the NIMA family of putative cell cycle regulators. CfNek is a protein of 479 amino acids that contains an unusual protein kinase domain that lacks the glycine-rich loop in subdomain I. The protein also harbours a PEST sequence and a pleckstrin homology domain. The tubulin polyglutamylase preparation displays the beta-casein phosphorylation activity typical for NIMA related kinases. Recombinant His-tagged CfNek expressed in Crithidia localises to the flagellar attachment zone/basal body of the parasite. After purification on a Ni(2+)-column the recombinant enzyme preparation displays ATP-dependent tubulin polyglutamylation activity as well as casein-phosphorylation activity.
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PMID:Identification of CfNek, a novel member of the NIMA family of cell cycle regulators, as a polypeptide copurifying with tubulin polyglutamylation activity in Crithidia. 1243 86

The "Down syndrome critical region" of human chromosome 21 has been defined based on the analysis of rare cases of partial trisomy 21. Evidence is accumulating that DYRK1A, one of the 20 genes located in this region, is an important candidate gene involved in the neurobiological alterations of Down syndrome. Both the structure of the DYRK1A gene and the sequence of the encoded protein kinase are highly conserved in evolution. The protein contains a unique assembly of structural motifs outside the catalytic domain, including a nuclear localization signal, a PEST region, and a repeat of 13 consecutive histidines. MNB/DYRK1A and related kinases are unique among serine/threonine-specific protein kinases in that their activity depends on tyrosine autophosphorylation in the catalytic domain. Also, evidence is accumulating that mRNA levels of MNB/DYRK1A are subject to tight regulation. A number of putative substrates of MNB/DYRK1A have emerged in the recent years, the majority of them being transcription factors. Although the function of MNB/DYRK1A in intracellular signalling and regulation of cell function is still poorly defined, current evidence suggests that the kinase may play a role in the regulation of gene expression.
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PMID:The MNB/DYRK1A protein kinase: genetic and biochemical properties. 1506 46

Cyclic AMP-dependent proteolysis of GATA-6(Delta50) was characterized using inhibitors for intracellular signaling pathways. Among these kinase inhibitors, only H-89 and K252a inhibited the proteolysis induced by dbcAMP, a membrane permeable cAMP analogue, others such as PD98059, SB203580, calphostine C, PP1, and KN-93 did not do so. These results suggest that A-kinase, but not C-kinase, MEK, P38 MAP-kinases or Src kinase, could participate in the observed phenomenon. We further demonstrated that an inhibitor for ubiquitin isopeptidase (Delta12-PGJ2) inhibited the degradation of GATA-6(Delta50) in the presence of dbcAMP, suggesting that the cAMP-dependent proteolysis could be mediated through the ubiquitin-proteasome pathway, although proteasome activity did not change significantly during dbcAMP treatment. The full-length GATA-6 was also responsive to the induced degradation. Furthermore, mutation of a potential phosphorylation site (Ser-290-->Ala) for A- and C-kinases, and deletion of the PEST sequence of GATA-6 did not abolish the degradation. All these results suggest that cellular factor(s) may play a crucial role in mediating the activation of the cAMP-dependent process.
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PMID:Characterization of cAMP-dependent proteolysis of GATA-6. 1591 46

Historically, the cAMP-dependent protein kinase (PKA) has a paradoxical role in cell motility, having been shown to both facilitate and inhibit actin cytoskeletal dynamics and cell migration. In an effort to understand this dichotomy, we show here that PKA is regulated in subcellular space during cell migration. Immunofluorescence microscopy and biochemical enrichment of pseudopodia showed that type II regulatory subunits of PKA and PKA activity are enriched in protrusive cellular structures formed during chemotaxis. This enrichment correlates with increased phosphorylation of key cytoskeletal substrates for PKA, including the vasodilator-stimulated phosphoprotein (VASP) and the protein tyrosine phosphatase containing a PEST motif. Importantly, inhibition of PKA activity or its ability to interact with A kinase anchoring proteins inhibited the activity of the Rac GTPase within pseudopodia. This effect correlated with both decreased guanine nucleotide exchange factor activity and increased GTPase activating protein activity. Finally, inhibition of PKA anchoring, like inhibition of total PKA activity, inhibited pseudopod formation and chemotactic cell migration. These data demonstrate that spatial regulation of PKA via anchoring is an important facet of normal chemotactic cell movement.
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PMID:Spatial regulation of the cAMP-dependent protein kinase during chemotactic cell migration. 1617 81

Kip-related proteins (KRPs) play a central role in the regulation of the cell cycle and differentiation through modulation of cyclin-dependent kinase (CDK) functions. We have identified a CDK inhibitor gene from Medicago truncatula (Mt) by a yeast two-hybrid screen. The KRPMt gene was expressed in all plant organs and cultured cells, and its transcripts accumulated after abscisic acid and NaCl treatment. The KRPMt protein exhibits seven conserved sequence domains and a PEST motif that is also detected in various Arabidopsis KRPs. In the yeast two-hybrid test, the KRPMt protein interacted with CDK (Medsa;CDKA;1) and D-type cyclins. However, in the pull-down assays, B-type CDK complexes were also detectable. Recombinant KRPMt differentially inhibited various alfalfa CDK complexes in phosphorylation assays. The immunoprecipitated Medsa;CDKA;1/A;2 complex was strongly inhibited, whereas the mitotic Medsa;CDKB2;1 complex was the most sensitive to inhibition. Function of Medsa;CDKB1;1 complex was not inhibited by the KRPMt protein. The mitotic Medsa;CYCB2 and Medsa;CYCA2;1 complexes responded weakly to this inhibitor protein. Kinase complexes from G2/M cells showed increased sensitivity towards the inhibitor compared with those isolated from G1/S-phase cells. In vitro phosphorylation of Medicago retinoblastoma-related protein was also reduced in the presence of KRPMt. Phosphorylation of this inhibitor protein by the recombinant calmodulin-like domain protein kinase (MsCPK3) resulted in enhanced inhibition of CDK function. The data presented emphasize the selective sensitivity of various cyclin-dependent kinase complexes to this inhibitor protein, and suggest a role for CDK inhibitors and CPKs in cross-talk between Ca2+ signalling and regulation of cell-cycle progression in plants.
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PMID:Activation of an alfalfa cyclin-dependent kinase inhibitor by calmodulin-like domain protein kinase. 1655 99

MST3 is a member of the sterile-20 protein kinase family with a unique preference for manganese ion as a cofactor in vitro; however, its biological function is largely unknown. Suppression of endogenous MST3 by small interference RNA enhanced cellular migration in MCF-7 cells with reduced expression of E-cadherin at the edge of migrating cells. The alteration of cellular migration and protruding can be rescued by RNA interference-resistant MST3. The expression of surface integrin and Golgi apparatus was not altered, but phosphorylation on tyrosine 118 and tyrosine 31 of paxillin was attenuated by MST3 small interfering RNA (siRNA). Threonine 178 was determined to be one of the two main autophosphorylation sites of MST3 in vitro. Mutant T178A MST3, containing alanine instead of threonine at codon 178, lost autophosphorylation and kinase activities. Overexpression of wild type MST3, but not the T178A mutant MST3, inhibited migration and spreading in Madin-Darby canine kidney cells. MST3 could phosphorylate the protein-tyrosine phosphatase (PTP)-PEST and inhibit the tyrosine phosphatase activity of PTP-PEST. We conclude that MST3 inhibits cell migration in a fashion dependent on autophosphorylation and may regulate paxillin phosphorylation through tyrosine phosphatase PTP-PEST.
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PMID:Inhibition of cell migration by autophosphorylated mammalian sterile 20-like kinase 3 (MST3) involves paxillin and protein-tyrosine phosphatase-PEST. 1704 25

The eukaryotic cell cycle is controlled by cyclin-dependent kinases (CDKs). Plants possess six types of CDK, among which the B-type CDK (CDKB) is expressed specifically from the late S- to the M-phase. We demonstrate that the expression of Arabidopsis CDKB2 is under the control of the protein degradation machinery. beta-Glucuronidase fused to a putative PEST motif of CDKB2 was unstable in tobacco Bright Yellow-2 cells and Arabidopsis plants, and its degradation was arrested by the proteasome inhibitor MG132. We propose that the abundance of CDKB2 protein is regulated not only at the transcriptional level, but also through proteasome-mediated protein degradation.
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PMID:Expression of B2-type cyclin-dependent kinase is controlled by protein degradation in Arabidopsis thaliana. 1709 23

Steroid receptor coactivators (SRCs) exert profound effects on animal development and physiology. These coactivators are nuclear proteins and transcription co-regulators that function to facilitate the transcription initiation mediated by nuclear receptors, as well as by other well-known transcription factors. However, how these co-regulators are functionally regulated is poorly understood. During genome-wide screening for SRC-interacting proteins, we identified a novel ankyrin repeat containing protein, SIP (SRC-Interacting Protein), which interacts with SRC coactivators in the cytoplasm. We demonstrated that extracellular stimuli such as the addition of estrogen, induced phosphorylation of SIP in its PEST (Proline, Glutamate, Serine, and Threonine rich) domain by casein kinase II. The phosphorylation of SIP resulted in dissociation of SRC proteins from SIP in the cytoplasm and led to subsequent nuclear translocation of SRC proteins and gene coactivation. Both gain-of-function and loss-of-function experiments indicate that SIP functions to sequester SRC coactivators in the cytoplasm and buffer the availability of these coactivators, thus providing a mechanism for the regulation of the transcription regulators.
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PMID:SIP, a novel ankyrin repeat containing protein, sequesters steroid receptor coactivators in the cytoplasm. 1747 5

The HPV16 E7 oncoprotein is an extended dimer, with a stable and cooperative fold, but that displays properties of "natively unfolded" proteins. Two regions of conserved sequence are found in E7 proteins, where the N-terminus (1-40) includes the retinoblastoma tumor suppressor binding and casein kinase II phosphorylation sites. A fragment containing the highly acidic N-terminal half shows an apparently disordered conformation by far-UV-circular dichroism (CD) at neutral pH, and its hydrodynamic radius is much larger than a neutral peptide of the same length. Trifluoroethanol and micellar concentrations of sodium dodecyl sulfate stabilize a much more helical structure at pH 4.0 than at pH 7.5, while submicellar concentrations of the detergent yield a beta-strand. The shape, pH, and temperature dependence of the CD spectrum at pH 7.5 are indicative of a poly proline type II structure. This structure is stabilized by phosphorylation, which would translate into increased transforming activity in the cell. Thus, the intrinsically disordered properties of the N-terminal module of E7 are responsible for the structural plasticity of the oncoprotein. Although the domain is not a compact and cooperatively folded unit, it is a bona fide functional domain, evolved to maintain a dynamic but extended structure in the cell. These properties allow adaptation to a variety of protein targets and expose the PEST degradation sequence that regulates its turnover in the cell, a modification of which leads to the accumulation of E7 species with consequences in the transformation process.
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PMID:The N-terminal module of HPV16 E7 is an intrinsically disordered domain that confers conformational and recognition plasticity to the oncoprotein. 1771 47


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