• it binds CDK2 during S phase, and CDK1 during the transition from G2 to M phase. (wikipedia.org)
  • Cyclin-dependent kinase 2 (Cdk2)/cyclin A is a novel PR coregulator that binds the NTD and acts by phosphorylating steroid receptor coactivator-1 and modulating steroid receptor coactivator-1 interaction with PR. (nih.gov)
  • The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. (affbiotech.cn)
  • In detail, CCNE (cyclin E, including CCNE1 and CCNE2) binds to CDK2, and subsequently phosphorylates Rb to promote G1-S progression. (biomedcentral.com)
  • A ) Levels of SAMHD1, phosphorylated SAMHD1, CDK1 and CDK2 proteins in activated or unsimulated, unfractionated PBMCs treated with carrier, AhR agonist or antagonist. (elifesciences.org)
  • B ) Levels of SAMHD1, phosphorylated SAMHD1, CDK1 and CDK2 proteins in activated or unstimulated purified CD4+ T cells treated with carrier, AhR agonist or antagonist. (elifesciences.org)
  • Binding of the ligand common to all Cks proteins, Cdk2, suppressed the conformational heterogeneity. (ens-lyon.fr)
  • CDK2 Protein is ideal for investigators involved in Signaling Proteins, Cell Cycle Proteins, Cancer, Cell Cycle, and Ser/Thr Kinases research. (rockland.com)
  • Given the observation that the inhibition requires Ran-GTP, a protein known to stabilize interactions between Crm1 and its target proteins, the authors hypothesize that Crm1, the phosphorylated MCM protein, and Ran-GTP form a heterotrimeric complex. (rupress.org)
  • M8 induces the expression of phosphorylated p53, proteins involved in the mismatch repair machinery (MSH6, MSH2, and MLH1) and a robust tail moment in a comet assay. (ccc.ac.at)
  • The active Cdk-cyclin complexes phosphorylate retinoblastoma proteins (pRb), enabling transcription of E2F-reponsive genes necessary for S-phase transition. (temple.edu)
  • A selectivity study done on 32 kinases showed that, compared with variolin B, meriolins display enhanced specificity toward CDKs, with marked potency on CDK2 and CDK9. (rcsb.org)
  • The profiling of compound 51 against a panel of 339 kinases revealed high selectivity for CDKs, with preference for CDK2 and CDK5 over CDK9, CDK1, CDK4, and CDK6. (proteopedia.org)
  • The kinase complex is able to phosphorylate CDK2 and CDC2 kinases, thus functions as a CDK-activating kinase (CAK). (novusbio.com)
  • Functions through the formation of specific serine/threonine protein kinase holoenzyme complexes with the cyclin-dependent protein kinases CDK1 or CDK2. (wuxibiortus.com)
  • Serine/Threonine Kinases (STKs), Cyclin-dependent protein kinase 2 (CDK2) and CDK3 subfamily, catalytic (c) domain. (umbc.edu)
  • The CDK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. (umbc.edu)
  • If these residues are inaccessible to kinases, how do they get phosphorylated then? (lu.se)
  • To confirm this we designed inhibitor-resistant (ir)-Cdk2 mutants using a novel bioinformatics approach. (rcsb.org)
  • Additionally, crystal structures and kinetics reveal alternative binding modes of Cdk1-selective and Cdk2-selective inhibitors and mechanisms of Cdk2 inhibitor resistance. (rcsb.org)
  • An integrated chemical biology approach provides insight into Cdk2 functional redundancy and inhibitor sensitivity. (expasy.org)
  • p27 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclin E-CDK2, which phosphorylates pRb, thereby ushering the cell from G1 into S phase through the Restriction point (Figure 2). (shu.edu)
  • CDK2 associates with and is regulated by the regulatory subunits of the complex including Cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A) and p27Kip1 (CDKN1B) (1). (rockland.com)
  • Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. (affbiotech.cn)
  • Subsequently, T cells receiving PD-1 signals displayed impaired Cdk2 activation and failed to phosphorylate two critical Cdk2 substrates, the retinoblastoma gene product (Rb) and the TGFβ-specific transcription factor Smad3 , leading to suppression of E2F target genes but enhanced Smad3 transactivation (Figure 3). (shu.edu)
  • CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. (umbc.edu)
  • We possess lately proven that phosphorylation of CDK9 at Ser90 by CDK2 alters CDK9 association with 7SE snRNP and unregulates HIV-1 transcription [25]. (healthyguide.info)
  • Despite that some of the CDK2 substrates are known, few of them display functions in meiosis. (lu.se)
  • Here, we investigate potential meiotic CDK2 substrates using in silico and in vitro approaches. (lu.se)
  • Our work has uncovered a few CDK2 substrates with meiotic functions, which will have to be verified in vivo. (lu.se)
  • A better understanding of the CDK2 substrates will help us to gain deeper insight into the functions of this universal kinase. (lu.se)
  • CDK2 phosphorylates multiple cellular substrates including SMAD3 and FOXO1. (rockland.com)
  • Fig. 2: p38γ compensates for the loss of CDK1 or CDK2. (nature.com)
  • Furthermore, CDK-activating kinase (CAK) phosphorylates cyclin-bound CDKs on a single threonine residue, a modification that is essential for their activity [ 6 - 9 ]. (biomedcentral.com)
  • Working in Xenopus egg extracts, the team found that, although the prevention of rereplication is dependent on high concentrations of Ran-GTP and Cdk2 kinase activity, it does not require nuclear export of MCM. (rupress.org)
  • Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA. (affbiotech.cn)
  • AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. (stjohnslabs.com)
  • Cyclin E/Cdk2 kinase activity is frequently deregulated in human cancers, resulting in impaired apoptosis. (oncotarget.com)
  • Subsequently, the type I receptor (ALK5) becomes phosphorylated by the type II receptor. (shu.edu)
  • When ubiquitinated, it translocates to the plasma membrane, where it becomes phosphorylated. (stjohnslabs.com)
  • A cyclin-dependent protein kinase holoenzyme complex that has a cyclin E2 regulatory subunit and a Cdk2 kinase subunit that has been phosphorylated. (proconsortium.org)
  • The cyclin subunit confers the substrate specificity of these complexes and differentially interacts with and activates CDK1 and CDK2 throughout the cell cycle. (wuxibiortus.com)
  • CDK2 is a catalytic subunit of the cyclin-dependent protein kinase complex, whose activity is restricted to the G1-S phase, and essential for cell cycle G1/S phase transition. (rockland.com)
  • Phosphorylation of CDC6 and MCM4 by the cyclin A2-CDK2 complex prevents re-replication of DNA during the cell cycle. (wikipedia.org)
  • Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. (proteopedia.org)
  • By inhibiting CDK1 and CDK2, roscovitine prevents cell routine development. (antiviralbiologic.com)
  • Phosphorylation at Ser-62 by CDK2 prevents Ras-induced senescence. (arigobio.com)
  • Cyclin E forms complexes during this interval with CDK2. (biomedcentral.com)
  • In G1-phase, Cdk4/6 and Cdk2 bind to and form complexes with D-type and E-type cyclins, respectively. (temple.edu)
  • Mathematical modeling of enzymology data predicted conditions allowing selective chemical Cdk2 inhibition. (rcsb.org)
  • Bypassing inhibition with ir-Cdk2 or with Cdk1 shows that Cdk2 is rate-limiting for replication in this system because Cdk1 is insufficiently active. (rcsb.org)
  • Cyclin A2 is synthesized at the onset of S phase and localizes to the nucleus, where the cyclin A2-CDK2 complex is implicated in the initiation and progression of DNA synthesis. (wikipedia.org)
  • The cyclin A2-CDK2 complex eventually phosphorylates E2F, turning off cyclin A2 transcription. (wikipedia.org)
  • 5 ns) molecular dynamics simulations indicate that residues of Cks1 that form the binding site for phosphorylated ligands are considerably more flexible in the free form of Cks1 than they are in the Cdk2-Cks1 complex. (ens-lyon.fr)
  • Ubiquitinated by the SCF(FBXW7) complex when phosphorylated at Thr-58 and Ser-62, leading to its degradation by the proteasome. (arigobio.com)
  • The CDK2/cyclin A complex plays a role in regulating DNA replication. (umbc.edu)
  • We hypothesize that a dynamic equilibrium between the dominant buried state and an transiently open, kinase-accessible state is present in the p27-cyclin A-CDK2 complex, and aim to test this hypothesis through the use of unbiased molecular dynamics and metadynamics simulations. (lu.se)
  • In addition, phosphorylated ERK1/2 and p38, key members of mitogen-activated protein kinase (MAPK) family regulating BCa tumorigenesis, were strongly decreased. (spandidos-publications.com)
  • however, phosphorylation of serine 400 was not required, indicating that JDP-2 and Cdk2/cyclin A act by distinct mechanisms. (nih.gov)
  • The final product is generated by affinity chromatography using a Rb-derived peptide that is phosphorylated at serine 249 and threonine 252. (abcam.cn)
  • During G1, cyclin D-dependent kinase-mediated phosphorylation of Rb at Ser-795 marks the conversion of Rb from a transcriptionally repressive, hypophosphorylated state to an inactive, phosphorylated state, which may be sustained through mitosis by differential phosphorylation of up to 16 putative serine or threonine residues. (affbiotech.com)
  • Cdk2 promotes DNA replication and is a promising cancer therapeutic target, but its functions appear redundant with Cdk1, an essential Cdk affected by most Cdk2 inhibitors. (rcsb.org)
  • Fig. 1: p38γ phosphorylates Rb and promotes liver proliferation after PHx. (nature.com)
  • It promotes the transition from G1 to S phase by phosphorylating and inactivating RB1. (rndsystems.com)
  • Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. (abcam.cn)
  • Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. (proteopedia.org)
  • Zhao J, Kennedy BK, Lawrence BD, Barbie DA, Matera AG, Fletcher JA, Harlow E. NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription. (proteopedia.org)
  • Studies with Mcl-1 phosphorylation mutants show that cyclin E/Cdk2-dependent phosphorylation of Mcl-1 residues on its PEST domain resulted in increased Mcl-1 stability (Thr92, and Thr163) and Bim binding (Ser64). (oncotarget.com)
  • How do buried residues get phosphorylated? (lu.se)
  • More generally, bioinformatics analyses have shown that ~15% of all phosphorylated residues are buried in the non-phosphorylated state, suggesting that transient exposure might be a general mechanism involved in protein regulation. (lu.se)
  • After the R point, pRb is phosphorylated and can no longer bind E2F, leading to cyclin A2 transcription. (wikipedia.org)
  • Here, CDK2 is involved in the regulation of meiotic transcription, the pairing of homologous chromosomes, and the maturation of meiotic crossover sites. (lu.se)
  • Phospho-p27 Kip1 (Thr198) Antibody detects endogenous levels of p27 Kip1 only when phosphorylated at Threonine 198. (affbiotech.cn)
  • When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome. (stjohnslabs.com)
  • We find that CDK2 phosphorylates PMS2 at Thr337, PMS1 at Thr331, and MLH1 in vitro. (lu.se)
  • Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. (umbc.edu)
  • Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. (umbc.edu)
  • CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. (umbc.edu)
  • We describe the development of highly potent diaminothiazole inhibitors of CDK2 (IC50 = 0.0009-0.0015 muM) from a single hit compound with weak inhibitory activity (IC50 = 15 muM), discovered by high-throughput screening. (proteopedia.org)
  • Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). (wuxibiortus.com)
  • A cooperative interaction between Cdk2 and Cks1 is suggested,which reduces the configurational entropy of Cks1 and therefore facilitates phosphoprotein binding. (ens-lyon.fr)
  • 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)
  • This phosphorylated form localizes to the cell membrane, where it is targeted by PDPK1 and PDPK2 for further phosphorylations on Thr-308 and Ser-473 leading to its activation. (stjohnslabs.com)
  • B ) Western blot analysis of STAT1 and phosphorylated STAT1 protein levels in macrophages treated with AhR agonist or antagonist and IFN-γ. (elifesciences.org)
  • B ) Western blot analysis of HSP90 (loading control) CDK1, cyclin A2, CDK2, cyclin E2 protein levels in macrophages treated with carrier (DMSO), AhR agonist or antagonist. (elifesciences.org)
  • C ) Western blot analysis of HSP90 (loading control), total SAMHD1 levels, and phosphorylated SAMHD1 levels in macrophages treated with carrier (DMSO), AhR agonist or antagonist. (elifesciences.org)
  • CDK2 Protein is suitable for use in Western Blot. (rockland.com)
  • Review: the total protein of unphosphorylated PI3K (t-PI3K), phosphorylated PI3K (p-PI3K), unphosphorylated AKT protein (t-AKT), and phosphorylated AKT protein (p-AKT) were detected and analysed using western blot in the presence of housekeeping protein β-Actin as a loading control at 4, 6, and 24 h intervals. (cusabio.com)
  • Together with experiments in Xenopus egg extracts, this supports a rate-limiting role for Cdk2 in DNA replication. (rcsb.org)
  • In testis extracts from mice lacking Cdk2, there are changes in expression of PMS2, MSH2, and HEI10, which may be reflective of the loss of CDK2 phosphorylation. (lu.se)
  • Structure-based design was performed using 35 cocrystal structures of CDK2 liganded with distinct analogues of the parent compound. (proteopedia.org)
  • It also blocks Cyclin A-CDK2 from further phosphorylating pRb to maintain S phase. (shu.edu)
  • Recombinant full-length human CDK2 was expressed by baculovirus in Sf9 insect cells using an N-Terminal Glutathione-S-Transferase fusion protein. (rockland.com)
  • Activated TNK2 phosphorylates it on Tyr-176 resulting in its binding to the anionic plasma membrane phospholipid PA. (stjohnslabs.com)
  • The Tyr-176 phosphorylated form shows a significant increase in expression in breast cancers during the progressive stages i.e. normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and lymph node metastatic (LNMM) stages. (stjohnslabs.com)
  • The phosphorylated form of PPP2R5B is required for bridging AKT1 with PP2A phosphatase. (stjohnslabs.com)