Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis C virus (HCV) is the major causative agent of hepatocellular carcinoma. However, the precise mechanism underlying the carcinogenesis is yet to be elucidated. It has recently been reported that Syk, a non-receptor protein tyrosine kinase, functions as a potent tumour suppressor in human breast carcinoma. This study first examined the possible effect of HCV infection on expression of Syk in vivo. Immunohistochemical analysis revealed that endogenous Syk, which otherwise was expressed diffusely in the cytoplasm of normal hepatocytes, was localized near the cell membrane with a patchy pattern in HCV-infected hepatocytes. The possible interaction between HCV proteins and Syk in human hepatoma-derived Huh-7 cells was then examined. Immunoprecipitation analysis revealed that NS5A interacted strongly with Syk. Deletion-mutation analysis revealed that an N-terminal portion of NS5A (aa 1-175) was involved in the physical interaction with Syk. An in vitro kinase assay demonstrated that NS5A inhibited the enzymic activity of Syk and that, in addition to the N-terminal 175 residues, a central portion of NS5A (aa 237-302) was required for inhibition of Syk. Moreover, Syk-mediated phosphorylation of phospholipase C-gamma1 was downregulated by NS5A. An interaction of NS5A with Syk was also detected in Huh-7.5 cells harbouring an HCV RNA replicon or infected with HCV. In conclusion, these results demonstrated that NS5A interacts with Syk resulting in negative regulation of its kinase activity. The results indicate that NS5A may be involved in the carcinogenesis of hepatocytes through the suppression of Syk kinase activities.
J Gen Virol 2008 May
PMID:Hepatitis C virus NS5A protein interacts with and negatively regulates the non-receptor protein tyrosine kinase Syk. 1842 Aug 2

Primary cultures of rainbow trout skeletal muscle cells were used to examine the role of insulin-like growth factor II (IGF-II) in fish muscle metabolism and growth, and to compare its main signal transduction pathways with those of IGF-I. IGF-II stimulated 2-deoxy-d-glucose (2-DG) uptake in trout myocytes at concentrations of between 5 and 100 nM, with similar maximal effects and temporal pattern to IGF-I (100 nM). The results of incubation with inhibitors (Wortmannin and CKB) indicated that IGF-II stimulates glucose uptake through the same mechanisms as IGF-I. In addition, IGF-II stimulated myoblast DNA synthesis (measured by thymidine incorporation) at relatively low concentrations (0.1-10 nM), with the maximum increase at 1 nM (167+/-17% with respect to control values). The cells were immunoreactive against ERK 1/2 MAPK and Akt/PKB, components of the two main signal transduction pathways for the IGF-I receptor. IGF-II stimulated the phosphorylation of the protein MAPK, especially at the proliferation stage (increases of up to 125.7+/-16.9% and 125.3+/-3.3% with respect to control in IGF-II- and IGF-I-treated cells, respectively). In contrast, the effects of both IGFs on the activation of the PI3K/Akt pathway were stronger in fully differentiated myocytes and in early-formed fibres (up to 359+/-18.5% in IGF-II-treated cells with respect to control). These results indicate that IGF-II has both mitogenic and metabolic effects in trout muscle cells, which are equivalent to those found in response to IGF-I. Both IGFs exert these effects though the same signalling pathways (MAPK and PI3K/Akt).
Gen Comp Endocrinol 2008 Jun
PMID:Metabolic and mitogenic effects of IGF-II in rainbow trout (Oncorhynchus mykiss) myocytes in culture and the role of IGF-II in the PI3K/Akt and MAPK signalling pathways. 1850 44

The extracellular calcium-sensing receptor (CaR) is expressed in various types of endocrine pituitary cell, but the intracellular mechanism this G protein-coupled receptor uses in these cells is not known. In the present study we investigated possible intracellular signal transduction pathway(s) utilized by the CaR of the endocrine melanotrope cells in the intermediate pituitary lobe of the South African-clawed toad Xenopus laevis. For this purpose, the effects of various pharmacological agents on CaR-evoked secretion of radiolabeled secretory peptides from cultured melanotrope cells were assessed. CaR-evoked secretion, induced by the potent CaR agonist L-phenylalanine (L-Phe), could not be inhibited by cholera toxin, nor by NPC-15437 and PMA, indicating that neither G(s)/PKA nor G(q)/PKC pathways are involved. However, pertussis toxin (G(i/o) protein inhibitor), genistein (inhibitor of PTKs), wortmannin/LY-294002 (PI3-K inhibitor) and U-0126 (inhibitor of extracellular signal-regulated kinase, ERK) all substantially inhibited CaR-evoked secretion, indicating that the Xenopus melanotrope cell possesses a PI3-K/MAPK system that plays some role in CaR-signaling. Since no direct effect of L-Phe on ERK phosphorylation could be shown it is concluded that CaR must act primarily through another, still unknown, signaling pathway in Xenopus melanotropes. Our results indicate that the PI3-K/MAPK system has a facilitating effect on CaR-induced secretion, possibly by sensitizing the CaR.
Gen Comp Endocrinol 2008 Jun
PMID:Intracellular signal transduction by the extracellular calcium-sensing receptor of Xenopus melanotrope cells. 1850 53

Latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV) provides developmental and survival signals that mimic those of a B-cell receptor (BCR). Expression of LMP2A during B-cell development results in the ability of B cells to exit the bone marrow in the absence of a BCR and persist in the periphery, where they would normally undergo apoptosis. This study extends the current knowledge of LMP2A function by examining the growth properties of bone marrow B cells from TgE LMP2A mice. Despite the lack of pre-BCR expression, bone marrow B cells from TgE LMP2A mice proliferate and survive in low concentrations of interleukin 7, similar to wild-type cells. Constitutive phosphorylation of ERK/MAPK and PI3K/Akt in TgE LMP2A bone marrow B cells is also reminiscent of signalling through the pre-BCR, altogether demonstrating that LMP2A provides a pre-BCR-like signal to developing B cells.
J Gen Virol 2008 Jul
PMID:EBV LMP2A provides a surrogate pre-B cell receptor signal through constitutive activation of the ERK/MAPK pathway. 1855 25

Mitogen-activated protein kinases (MAPKs) are important regulators of aryl hydrocarbon receptor (AhR). An immense progress in MAPKs' biochemistry was attained with the discovery of their specific pharmacological inhibitors. Unfortunately, the inhibitors of JNK and ERK MAPKs, i.e. SP600125 and U0126, respectively, affect AhR-CYP1A signaling pathway because they are partial agonists of AhR and induce CYP1A genes. This implies that SP600125 and U0126 are inappropriate tools for studies of the role of MAPKs in AhR regulation. The results from studies using SP600125 or U126, past or future, should be interpreted with prudence regarding their stimulatory effects on AhR-CYP1A pathway.
Gen Physiol Biophys 2008 Jun
PMID:Pharmacological inhibitors of JNK and ERK kinases SP600125 and U0126 are not appropriate tools for studies of drug metabolism because they activate aryl hydrocarbon receptor. 1864 29

BRCA1-associated protein 2 (BRAP2) is known to interact with the kinase suppressor of Ras 1 (KSR1), inhibiting the ERK signal transduction cascade. This study found that an Epstein-Barr virus (EBV) immediate-early protein, Rta, is a binding partner of BRAP2 in yeast and confirmed the binding in vitro by a glutathione S-transferase pull-down assay and in vivo by co-immunoprecipitation in 293(maxi-EBV) cells. Binding studies also showed that Rta and KSR1 interacted with the C-terminal 202 aa region in BRAP2. Additionally, Rta appeared to prevent the binding of KSR1 to BRAP2, activating the ERK signal transduction pathway and the transcription of an EBV immediate-early gene, BZLF1. Activation of the ERK signal transduction pathway by Rta may be critical for the maintenance of the lytic state of EBV.
J Gen Virol 2008 Oct
PMID:Activation of the ERK signal transduction pathway by Epstein-Barr virus immediate-early protein Rta. 1879 11

In teleosts, gonadotropin (GTH) secretion and synthesis is controlled by multiple neuroendocrine factors from the hypothalamus, pituitary and peripheral sources. Pituitary gonadotropes must be able to differentiate and integrate information from these regulators at the cellular and intracellular level. In this article, the intracellular signal transduction mechanisms mediating the actions of some of these regulators, including GTH-releasing hormones, pituitary adenylate cyclase-activating polypeptide, dopamine, ghrelin, sex steroids, activin, and follistatin from experiments with goldfish are reviewed and discussed in relation with recent findings. Information from other teleost models is briefly compared. Goldfish gonadotropes possess multiple pharmacologically distinct intracellular Ca2+ stores that together with voltage-sensitive Ca2+ channels, Na+/H+ exchangers, protein kinase C, arachidonic acid, NO, protein kinase A, ERK/MAPK, and Smads allows for integrated control by different neuroendocrine factors.
Gen Comp Endocrinol 2009 Mar
PMID:Signal transduction in multifactorial neuroendocrine control of gonadotropin secretion and synthesis in teleosts-studies on the goldfish model. 1883 74

This review addresses the control exerted by insulin through its receptor on the general metabolism and gene expression in chicken liver and muscle. Compared with mammals, chickens have similar concentrations of circulating insulin, but still maintain high plasma glucose levels. This may be a consequence of the low sensitivity of the chicken to exogenous insulin. In order to determine whether this low sensitivity is the result of differences in insulin receptor signaling between mammals and birds, insulin receptors have been characterized in several chicken tissues and two insulin receptor substrates (IRS-1 and Shc) have been described in liver and muscle. Compared with mammals current knowledge of insulin signaling in birds is incomplete. This is particularly evident when considering the number of isoforms of the components involved in the insulin cascade (IRSs, AKT, ERK and others) many of which may have not been characterized in the chicken. Despite these shortfalls in available data, it appears that insulin signaling in chicken liver is similar to that in mammals, but is unlike that in mammals in muscle. In leg muscle, chickens differ from mammals in the early steps of the insulin signaling cascade (IR, IRS-1 and PI3K) where PI3K activity is about 30-fold greater in the chicken than in the rat. This "constitutive" hyperactivity of PI3K in chicken muscle may over-stimulate a feedback inhibitory pathway described in mammals thereby desensitizing chicken muscle to insulin.
Gen Comp Endocrinol 2009 Sep 01
PMID:Insulin signaling in chicken liver and muscle. 1899 26

The influenza virus RNA polymerase transcribes the negative-sense viral RNA segments (vRNA) into mRNA and replicates them via complementary RNA (cRNA) intermediates into more copies of vRNA. It is not clear how the relative amounts of the three RNA products, mRNA, cRNA and vRNA, are regulated during the viral life cycle. We found that in viral ribonucleoprotein (vRNP) reconstitution assays involving only the minimal components required for viral transcription and replication (the RNA polymerase, the nucleoprotein and a vRNA template), the relative levels of accumulation of RNA products differed from those observed in infected cells, suggesting a regulatory role for additional viral proteins. Expression of the viral NS2/NEP protein in RNP reconstitution assays affected viral RNA levels by reducing the accumulation of transcription products and increasing the accumulation of replication products to more closely resemble those found during viral infection. This effect was functionally conserved in influenza A and B viruses and was influenza-virus-type-specific, demonstrating that the NS2/NEP protein changes RNA levels by specific alteration of the viral transcription and replication machinery, rather than through an indirect effect on the host cell. Although NS2/NEP has been shown previously to play a role in the nucleocytoplasmic export of viral RNPs, deletion of the nuclear export sequence region that is required for its transport function did not affect the ability of the protein to regulate RNA levels. A role for the NS2/NEP protein in the regulation of influenza virus transcription and replication that is independent of its viral RNP export function is proposed.
J Gen Virol 2009 Jun
PMID:NS2/NEP protein regulates transcription and replication of the influenza virus RNA genome. 1926 57

Previously, we identified a cellular kinase inhibitor, GW5074, that inhibits poliovirus (PV) and enterovirus 71 replication strongly, although its target has remained unknown. To identify the target of GW5074, we searched for cellular kinase inhibitors that have anti-enterovirus activity similar or related to that of GW5074. With this aim, we performed screenings to identify cellular kinase inhibitors that could inhibit PV replication cooperatively with GW5074 or synthetically in the absence of GW5074. We identified MEK1/2 inhibitors (SL327 and U0126), an EGFR inhibitor (AG1478) and a phosphatidylinositol 3-kinase inhibitor (wortmannin) as compounds with a cooperative inhibitory effect with GW5074, and an Akt1/2 inhibitor (Akt inhibitor VIII) as a compound with a synthetic inhibitory effect with MEK1/2 inhibitors and AG1478. Individual treatment with the identified kinase inhibitors did not affect PV replication significantly, but combined treatment with MEK1/2 inhibitor, AG1478 and Akt1/2 inhibitor suppressed the replication synthetically. The effect of AG1478 in this synthetic inhibition was compensated by other receptor tyrosine kinase inhibitors (IGF-1R inhibitor II and Flt3 inhibitor II). We isolated mutants resistant to Flt3 inhibitor II and GW5074 and found that these mutants had cross-resistance to each treatment. These mutants had a common mutation in viral protein 3A that results in an amino acid change at position 70 (Ala to Thr), a mutation that was previously identified in mutants resistant to a potent anti-enterovirus compound, enviroxime. These results suggest that cellular kinase inhibitors and enviroxime have a conserved target in viral protein 3A to suppress enterovirus replication.
J Gen Virol 2009 Aug
PMID:Cellular kinase inhibitors that suppress enterovirus replication have a conserved target in viral protein 3A similar to that of enviroxime. 1943 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>