• Here we compare the specificity of two budding yeast cyclins, the S-phase cyclin Clb5 and the M-phase cyclin Clb2, in the phosphorylation of 150 Cdk1 (Cdc28) substrates. (nature.com)
  • Phosphorylation of Clb5-specific targets during S phase was reduced by replacing Clb5 with Clb2 or by mutating the substrate RXL motif, confirming the importance of Clb5 specificity in vivo . (nature.com)
  • Although we did not identify any highly Clb2-specific substrates, we found that Clb2-Cdk1 possessed higher intrinsic kinase activity than Clb5-Cdk1, enabling efficient phosphorylation of a broad range of mitotic Cdk1 targets. (nature.com)
  • Thus, Clb5 and Clb2 use distinct mechanisms to enhance the phosphorylation of S-phase and M-phase substrates. (nature.com)
  • Figure 3: Clb5-specific substrate phosphorylation occurs in vivo . (nature.com)
  • Protein phosphorylation catalyzed by kinases plays crucial roles in regulating a variety of intracellular processes. (nih.gov)
  • In this update, we not only enhance the data content in human but also investigate kinase-substrate phosphorylation networks in mouse and rat. (nih.gov)
  • The experimentally validated phosphorylation sites as well as their catalytic kinases were extracted from public resources, and MS/MS phosphopeptides were manually curated from research articles. (nih.gov)
  • This positional scanning synthetic peptide combinatorial library (PS-SPCL) has been used in rapid identification of serine/threonine kinase phosphorylation motif. (anaspec.com)
  • Liu Y, Zhang S (2004) Phosphorylation of 1-aminocyclopropane-1-carboxylic acid synthase by MPK6, a stress-responsive mitogen-activated protein kinase, induces ethylene biosynthesis in Arabidopsis . (springer.com)
  • 2016). Here, we expand this high-throughput platform to analyze the intrinsic specificity of any tyrosine kinase domain against thousands of peptides derived from human tyrosine phosphorylation sites. (escholarship.org)
  • The Pim family of serine/threonine protein kinases (Pim 1, 2, and 3) contribute to cellular transformation by regulating glucose metabolism, protein synthesis, and mitochondrial oxidative phosphorylation. (oncotarget.com)
  • To identify novel substrates, bioinformatics analysis was carried out to identify proteins containing a consensus Pim phosphorylation site. (oncotarget.com)
  • G protein-coupled receptor kinases (GRKs) control the signaling and activation of G protein-coupled receptors through phosphorylation. (elsevierpure.com)
  • In this study, we revealed that Homer3 was phosphorylated by calcium/calmodulin-dependent protein kinase II (CaMKII) in Purkinje cells, and the phosphorylation reduces the affinity for Homer target molecules, resulting in change of the solubility. (jneurosci.org)
  • This Tks5-reliant increase in intrusive behavior additional depended on Src tyrosine kinase activity as well as the phosphorylation of Tks5 at tyrosine residues 557 and 619. (healthanddietblog.info)
  • Here, we mechanically extended bacterially expressed Cas substrate domain protein (CasSD) in vitro and found a remarkable enhancement of phosphorylation by Src family kinases with no apparent change in kinase activity. (utmb.edu)
  • BACKGROUND: Control of intracellular events by protein phosphorylation is promoted by specific protein kinases. (ox.ac.uk)
  • Phk gamma trnc is constitutively active, and lacks the need for an activatory phosphorylation event that is essential for many kinases. (ox.ac.uk)
  • Histidine-protein kinases function in partnership with cognate response-regulator substrate(s): usually transcription factors that they activate by phosphorylation. (elsevierpure.com)
  • Testis-specific serine kinase 3 (Tssk3) is a conserved gene, but TSSK3 kinase functions and phosphorylation substrates of TSSK3 are not known. (cdc.gov)
  • We demonstrate that DARPP-32 inhibits MCF-7 cell migration and that this effect requires phosphorylation of Threonine-34, an event catalyzed by protein kinase A (PKA) and strongly induced by detachment of cells from the culture substrate. (lu.se)
  • Clb5 specificity depended on an interaction between a hydrophobic patch in Clb5 and a short sequence in the substrate (the RXL or Cy motif). (nature.com)
  • Figure 2: Clb5 specificity depends on an interaction between the Clb5 hydrophobic patch and an RXL motif in the substrate. (nature.com)
  • A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. (nature.com)
  • Brown, N. R., Noble, M. E., Endicott, J. A. & Johnson, L. N. The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases. (nature.com)
  • Tested against a panel of 96 kinases, TAK-285 showed specificity for inhibition of HER family kinases. (jcancer.org)
  • Human herpesvirus 8 open reading frame 21 is a thymidine and thymidylate kinase of narrow substrate specificity that efficiently phosphorylates zidovudine but not ganciclovir. (umassmed.edu)
  • The specificity of tyrosine kinases is attributed predominantly to localization effects dictated by non-catalytic domains. (escholarship.org)
  • These results point to the importance of direct recognition at the kinase active site in fine-tuning specificity. (escholarship.org)
  • A systematic study was undertaken in order to assess the substrate specificity of cyclin-B/cell division control protein kinase (CDC2) isolated from human HeLa cells, using 13-15 residue peptides with a central histone-like KKSPKK motif as a model. (unityfvg.it)
  • Within this common structural framework each kinase displays its own unique substrate specificity, and a regulatory mechanism that may be modulated by association with other proteins. (ox.ac.uk)
  • Substrate specificity is a fundamental property that determines the specificity and fidelity of signaling by protein tyrosine kinases. (johnshopkins.edu)
  • This model may provide a framework for understanding substrate recognition and specificity of other protein tyrosine kinases. (johnshopkins.edu)
  • In this study, consensus substrate motifs for GRK2 were identified from the sequences of GRK2 protein substrates, and 17 candidate peptides were synthesized to identify peptide substrates with high affinity for GRK2. (elsevierpure.com)
  • These peptides are potential substrates of EGFR protein tyrosine kinase. (bestbiochem.com)
  • PKA is also known as cAMP-dependent protein kinase (EC 2.7.11.11). (wikipedia.org)
  • The following human genes encode PKA subunits: catalytic subunit - PRKACA, PRKACB, PRKACG regulatory subunit type I - PRKAR1A, PRKAR1B regulatory subunit type II - PRKAR2A, PRKAR2B PKA is also commonly known as cAMP-dependent protein kinase, because it has traditionally been thought to be activated through release of the catalytic subunits when levels of the second messenger called cyclic adenosine monophosphate, or cAMP, rise in response to a variety of signals. (wikipedia.org)
  • Phk gamma trnc) of the gamma-subunit of rabbit muscle phosphorylase kinase: the binary complex with Mn2+/beta-gamma-imidoadenosine 5'-triphosphate (AMPPNP) to a resolution of 2.6 A and the binary complex with Mg2+/ADP to a resolution of 3.0 A. The structures were solved by molecular replacement using the cAMP-dependent protein kinase (cAPK) as a model. (ox.ac.uk)
  • Bidirectional regulation of signal transduction by protein kinase C (PKC) and the cAMP-dependent protein kinase (PKA) have been observed in neuronal and inflammatory cells. (cdc.gov)
  • The kinases are represented in complex with an ATP molecule (green, orange, blue, red) and a substrate-mimicking inhibitor (PKIA, yellow). (plos.org)
  • We investigated the effects of TAK-285, a novel, investigational, dual EGFR/HER2 inhibitor that has been shown to penetrate the CNS and has comparable inhibitory efficacy to lapatinib which is a known Pgp substrate. (jcancer.org)
  • These results demonstrate that IRS1 S1101 is a novel substrate for the Pim kinases and provide a novel marker for evaluation of Pim inhibitor therapy. (oncotarget.com)
  • and liver fibrosis resolved on treatment with the Src kinase inhibitor dasatinib. (nature.com)
  • Two patients with truncating mutations had liver fibrosis that in one patient resolved on treatment with the Src kinase inhibitor dasatinib. (nature.com)
  • Protein tyrosine kinases are key enzymes of mammalian signal transduction. (johnshopkins.edu)
  • The ↑[Ca 2+ ] i activates a signaling cascade that involves, sequentially, calcium-calmodulin, nitric oxide synthase, guanylyl cyclase, and protein kinase G. This signal transduction pathway enables Cl − to pass through vesicular channels and act as a counterion for the transport of H + , so that the vesicles of secretogogue-stimulated cells become acidic. (jneurosci.org)
  • ZAT10 was phosphorylated by recombinant Arabidopsis MPK3 and MPK6 in a kinase assay. (springer.com)
  • Furthermore, ZAT10 was also phosphorylated by native MPK3 and MPK6 prepared from Arabidopsis plants in an in-gel kinase assay. (springer.com)
  • Farrar, YJK, Vanaman, TC & Slevin, JT 1991, ' A phosphatase resistant substrate for the assay of protein kinase C in crude tissue extracts ', Biochemical and Biophysical Research Communications , vol. 180, no. 2, pp. 694-701. (uky.edu)
  • Primary bovine bronchial epithelial cells were grown in culture and assayed for PKA and PKC activity using a direct specific substrate radiolabeled-phosphate incorporation assay. (cdc.gov)
  • Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
  • moreover, PI3′-kinase inhibitors (wortmannin and LY294002) antagonized secretion. (jneurosci.org)
  • HMG-CoA inhibitors, also known as statins, are linked to an exposure-related risk for myopathy that presents as muscle pain, tenderness, or weakness, with elevated creatine kinase levels greater than 10 times the upper limit of normal. (medscape.com)
  • Because statins are substrates for the cytochrome P450 isoenzyme 3A4 (CYP3A4), concomitant use of CYP3A4 inhibitors (eg, indinavir and other protease inhibitors) can increase plasma concentrations and the attendant risk for myopathy. (medscape.com)
  • abstract = "Protein kinase C (PKC) is routinely assayed, after it is partially purified over DEAE-cellulose chromatography to eliminate any interfering protein kinases and phosphatases, by measuring the transfer of γ-phosphate of [γ-32P]ATP to Hl histone. (uky.edu)
  • This peptide is a potential substrate for EGFR protein tyrosine kinases. (anaspec.com)
  • We developed a method to profile the specificities of tyrosine kinases by combining bacterial surface-display of peptide libraries with next-generation sequencing. (escholarship.org)
  • Though they talk about a number of the same cytoskeletal regulatory equipment (integrins tyrosine kinases Arp2/3 WASp) as additional adhesion constructions they are recognized by marker protein CK-1827452 (Omecamtiv mecarbil) (cortactin dynamin2 Tks5) and metalloproteinases (MT1-MMP) that distinctively support focalized matrix redesigning activity [2-5]. (healthanddietblog.info)
  • Src may be the namesake person in a grouped category of non-receptor tyrosine kinases as well as the initial described protooncogene [7]. (healthanddietblog.info)
  • However, how protein tyrosine kinases recognize the protein substrates is not well understood. (johnshopkins.edu)
  • Query proteins are circled, kinase proteins are colored as pink and non-kinase proteins are colored by light green. (phosphonetworks.org)
  • Once released from inhibitory regulatory subunit, the catalytic subunits can go on to phosphorylate a number of other proteins in the minimal substrate context Arg-Arg-X-Ser/Thr. (wikipedia.org)
  • BACKGROUND The Src tyrosine kinase substrate and adaptor proteins Tks5 had previously been implicated in the invasive phenotype of normal and transformed cell types via rules of cytoskeletal constructions called podosomes/invadopodia. (healthanddietblog.info)
  • Src activation also frequently promotes podosome/invadopod development [4 11 That is backed by the current presence of tyrosine phosphorylated proteins at these constructions many of that are Src substrates [14-18]. (healthanddietblog.info)
  • Tks5 is a substrate of Src and an adaptor protein for proteins and lipids [19]. (healthanddietblog.info)
  • Primer recognition proteins (PRP) stimulate the activity of DNA polymerase α on DNA substrates with long single-stranded template containing few primers. (nebraska.edu)
  • Heme-based sensors are a recently discovered functional class of heme proteins that serve to detect physiological fluctuations in oxygen (O 2 ), carbon monoxide (CO), or nitric oxide (NO). Many of these modular sensors detect heme ligands by coupling a histidine-protein kinase to a heme-binding domain. (elsevierpure.com)
  • The use of this Group II of distinct 18 peptide mixtures, in combination with Group I of 180 distinct peptide mixtures (cat# 62017-1), can provide sequence preference information of different kinases. (anaspec.com)
  • Kovtun Y, Chiu WL, Tena G, Sheen J (2000) Functional analysis of oxidative stress-activated mitogen-activated protein kinase cascade in plants. (springer.com)
  • MAPK-Group (2002) Mitogen-activated protein kinase cascades in plants: a new nomenclature. (springer.com)
  • Rapid determination of multiple linear kinase substrate motifs by mass spectrometry. (kettenbachlab.org)
  • Two structures of the catalytic domain of phosphorylase kinase: an active protein kinase complexed with substrate analogue and product. (ox.ac.uk)
  • Structural studies of phosphorylase kinase (Phk), the major substrate of which is glycogen phosphorylase, may be expected to shed light on its regulation. (ox.ac.uk)
  • Crystallographic studies on adenylate kinase (AK) suggest that binding of ATP causes the LID domain of the enzyme to close over the ATP molecule (Schlauderer et al. (psu.edu)
  • Cytotoxic effects of fipronil and fipronil sulfone were examined using the adenylate kinase and the trypan blue exclusion assays in HepG2 cells and human hepatocytes. (cdc.gov)
  • The maximum induction of adenylate kinase was ca. 3-fold greater than the respective controls in HepG2 and 6-10-fold in the case of primary hepatocytes. (cdc.gov)
  • A significant time- and dose-dependent induction of adenylate kinase activity in HepG2 cells was noted from 0.1 to 12.5 µM fipronil followed by decreasing activities at 25 and 50 µM. (cdc.gov)
  • These sites were verified by site-directed mutagenesis and in vitro kinase assays. (springer.com)
  • Using this, we showed that the tyrosine kinase ZAP-70, which is critical for T cell signaling, discriminates substrates through an electrostatic selection mechanism encoded within its catalytic domain (Shah et al. (escholarship.org)
  • Although both Csk and MAP kinases used docking sites for substrate recognition, their docking sites consisted of different substructures in the catalytic domain. (johnshopkins.edu)
  • Our study demonstrates in both malignant and normal cells using either genetic or pharmacological inhibition of the Pim kinases or overexpression of this family of enzymes that human IRS1 S1101 and IRS2 S1149 are Pim substrates. (oncotarget.com)
  • Closure of the LID domain in response to AMP binding may be a possible reason for the strong AMP-substrate inhibition known for E. coli AK. (psu.edu)
  • PKC involvement can be accounted for by PKCγ and an isoform sensitive to inhibition by pseudoZ, probably PKCζ, which is activated via PI3′-kinase. (jneurosci.org)
  • We found that Homer3, the predominant isoform in Purkinje cells, is phosphorylated by calcium/calmodulin-dependent protein kinase II (CaMKII) both in vitro and in vivo . (jneurosci.org)
  • Here, we investigate potential meiotic CDK2 substrates using in silico and in vitro approaches. (lu.se)
  • A similar mechanism was confirmed for Csk recognition of another Src family kinase, Yes. (johnshopkins.edu)
  • These results helped establish a docking-based substrate recognition mechanism for Csk. (johnshopkins.edu)
  • Our studies suggest that investigational drugs such as TAK-285 that have strong antitumor activity and are not Pgp substrates may be useful in the development of agents with the potential to treat brain metastases. (jcancer.org)
  • The goal of these studies was to identify Pim substrate(s) that could help define the pathway regulated by these enzymes and potentially serve as a biomarker of Pim activity. (oncotarget.com)
  • We characterize the role of increased Lyn kinase activity in neutrophils, endothelial cells and lesional liver biopsies and utilized an iPSC-derived endothelial cell platform for disease modeling of neutrophilic vasculitis and to screen and evaluate drug efficacy. (nature.com)
  • In cell biology, protein kinase A (PKA) is a family of serine-threonine kinase whose activity is dependent on cellular levels of cyclic AMP (cAMP). (wikipedia.org)
  • The aims of this thesis have been to investigate the regulation and function of the centrosomal kinase Nek2, which has previously been implicated in regulating centrosome cohesion at G2/M. Nck2 kinase activity is regulated by a number of mechanisms, including autophosphorylation and interaction with protein phosphatase 1. (le.ac.uk)
  • Src is generally upregulated in advanced stage malignancies and activation of Src tyrosine kinase activity transforms cells to a neoplastic phenotype with improved survival development and migration [8-10]. (healthanddietblog.info)
  • By molecular docking and site-directed mutagenesis , we rationally engineered the dual-substrate channel cavity of polyphosphate kinase to improve the catalytic activity of PPK. (bvsalud.org)
  • Predicted to enable protein kinase regulator activity. (wormbase.org)
  • Predicted to enable ATP binding activity and MAP kinase activity. (wormbase.org)
  • Likewise, activity levels for a CYP1A1-specific substrate, luciferin CEE, demonstrated that CYP1A1 enzyme activities were maximally induced by 1 µM fipronil followed by dramatically declining activity measurements at 10 and 25 µM. (cdc.gov)
  • Finally, we found that phospho-DARPP-32 inhibited the activity of the focal adhesion kinase (FAK) in MCF-7 breast cancer cells, and that MCF-7 cells expressing phospho-DARPP-32 displayed less filopodia formation. (lu.se)
  • Choline kinase alpha (ChoKalpha) is an enzyme involved in the metabolism of phospholipids recently found to play a relevant role in the regulation of cell proliferation, oncogenic transformation and human carcinogenesis. (nih.gov)
  • Increasing the ability of ChPPK enzyme to produce ATP can effectively enhance the conversion rate of substrate and reduce the catalytic cost , achieving high yield, high conversion rate and high economic value for glutathione production by cell -free catalysis . (bvsalud.org)
  • By amino acid sequence homology, we have identified PRP 2 as the glycolytic enzyme 3-phosphoglycerate kinase. (nebraska.edu)
  • C-terminal Src kinase (Csk) specifically phosphorylates Src family kinases on a C-terminal Tyr residue, which down-regulates their activities. (johnshopkins.edu)
  • Fisher, D. L. & Nurse, P. A single fission yeast mitotic cyclin B p34 cdc2 kinase promotes both S-phase and mitosis in the absence of G1 cyclins. (nature.com)
  • With an attempt to help users efficiently identify the candidate biomarkers in cancers, 30 microarray experiments, including 39 cancerous versus normal cells, were analyzed for detecting cancer-specific expressed genes coding for kinases and their substrates. (nih.gov)
  • Using this approach, we find a difference in the electrostatic recognition of substrates between the closely related Src-family kinases Lck and c-Src. (escholarship.org)
  • In the current study, we identified the docking determinants in Src recognized by the Csk substrate-docking site and demonstrated an interaction between the docking determinants of Src and the Csk substrate-docking site for this recognition. (johnshopkins.edu)
  • Increased DVL levels, in contrast, sequester centrosomal NEK2 and mimic monopolar spindle defects induced by a dominant negative version of this kinase. (muni.cz)
  • Extracellular hormones, such as glucagon and epinephrine, begin an intracellular signalling cascade that triggers protein kinase A activation by first binding to a G protein-coupled receptor (GPCR) on the target cell. (wikipedia.org)
  • The mammalian target of rapamycin (mTOR) is an evolutionarily highly conserved intracellular serine/threonine kinase family member. (hindawi.com)
  • DVL accumulates during the cell cycle and associates with NIMA-related kinase 2 (NEK2), which is able to phosphorylate DVL at amultitude of residues, as detected by a set of novel phospho-specific antibodies. (muni.cz)
  • PF cells were found to express regulatory (p85) and catalytic (p110α and p110β) subunits of phosphatidylinositol 3′-kinase (PI3′-kinase). (jneurosci.org)
  • This analysis identified the insulin receptor substrate 1 and 2 (IRS1/2) as potential Pim substrates. (oncotarget.com)
  • Moreover, Wnt-5a is known to inhibit migration of breast epithelial cells in culture and expression of Wnt-5a potentiates activation of the receptor tyrosine kinase DDR1, a collagen receptor implicated in cell adhesion and migration. (lu.se)
  • out of 540 different protein kinase genes that make up the human kinome, only one other protein kinase, casein kinase 2, is known to exist in a physiological tetrameric complex, meaning it consists of four subunits. (wikipedia.org)
  • The molecular basis to understand the connection between phospholipids metabolism and cell cycle regulation through choline kinase is reported. (nih.gov)
  • Adenosine monophosphate-activated protein kinase activation, substrate transporter translocation, and metabolism in the contracting hyperthyroid rat heart. (ox.ac.uk)
  • Thyroid hormones can modify cardiac metabolism via multiple molecular mechanisms, yet their integrated effect on overall substrate metabolism is poorly understood. (ox.ac.uk)
  • Here we determined the effect of hyperthyroidism on substrate metabolism in the isolated, perfused, contracting rat heart. (ox.ac.uk)
  • Cyclin dependent-kinase 2 (CDK2) plays important functions during the mitotic cell cycle and also facilitates several key events during germ cell development. (lu.se)
  • A rabbit polyclonal anti-chicken calpactin I antibody was shown to cross-react with PRP 1 polypeptide at various stages of PRP purification, and the homogeneous preparation of PRP exhibits 3-phosphoglycerate kinase (PRP 2) and calpactin I (PRP 1) activities. (nebraska.edu)
  • Aggregated analysis of sequence divergence across kinase families (left) and subfamilies (right). (plos.org)
  • Middle) Total number of switches mapped to the kinase primary sequence, with secondary structure elements represented above the bar plot. (plos.org)
  • The phosphorylated residue that is located at the domain interface in many protein kinases and that is believed to stabilize an active conformation is substituted by a glutamate in Phk gamma trnc. (ox.ac.uk)
  • The glutamate, in a similar manner to the phosphorylated residue in other protein kinases, interacts with an arginine adjacent to the catalytic aspartate but does not participate in interdomain contacts. (ox.ac.uk)
  • Our work has uncovered a few CDK2 substrates with meiotic functions, which will have to be verified in vivo. (lu.se)
  • Droillard M, Boudsocq M, Barbier-Brygoo H, Lauriere C (2002) Different protein kinase families are activated by osmotic stresses in Arabidopsis thaliana cell suspensions. (springer.com)
  • Rational design of polyphosphate kinase dual-substrate channel cavity for efficient production of glutathione by cell free catalysis]. (bvsalud.org)
  • Is an ortholog of human MAK (male germ cell associated kinase). (wormbase.org)
  • Bethke G, Unthan T, Uhrig JF, Poschl Y, Gust AA, Scheel D, Lee J (2009) Flg22 regulates the release of an ethylene response factor substrate from MAP kinase 6 in Arabidopsis thaliana via ethylene signaling. (springer.com)
  • We investigate the hypothesis that the action of chronic lithium on PKC isozymes and substrates may be secondary to its potent effect in inhibiting the recycling of inositol. (unboundmedicine.com)
  • Next-generation sequencing identified two de novo truncating variants in the Src-family tyrosine kinase, LYN , p.Y508*, p.Q507* and a de novo missense variant, p.Y508F, that result in constitutive activation of Lyn kinase. (nature.com)
  • A role of Src family kinase members in causing sterile inflammation and human disease is only recently recognized. (nature.com)
  • Protein kinase A, more precisely known as adenosine 3',5'-monophosphate (cyclic AMP)-dependent protein kinase, abbreviated to PKA, was discovered by chemists Edmond H. Fischer and Edwin G. Krebs in 1968. (wikipedia.org)
  • Is an ortholog of human KIDINS220 (kinase D interacting substrate 220). (wormbase.org)
  • SILAC kinase screen identifies potential MASTL substrates. (edu.au)
  • Calpactin I and 3-phosphoglycerate kinase, purified independently, cannot be efficiently reconstituted into the PRP complex, indicating that their association in the PRP complex involves specific protein-protein interactions that remain to be elucidated. (nebraska.edu)