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

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The AP-1 transcription factor, which is composed of various combinations of Fos and Jun proteins, is believed to be a key participant in molecular processes that guide activity-dependent changes in gene expression. In this study, we investigated the activity of different MAP kinases that have been implicated in AP-1 activation. We examined the activities of ERK, JNK/SAPK, and p38 MAPK along with their nuclear targets (Elk-1 and c-Jun) in rat visual cortex after light stimulation. The transcription factor Elk-1 (a possible regulator of c-fos expression) was found to be transiently modified by phosphorylation when visual stimulation was applied after a period of dark rearing. In vitro kinase assay with Elk-1 as substrate showed that light stimulation activated MAPK/ERK in visual cortex but not frontal cortex. Furthermore, ERK activation was temporally matched to onset of Elk-1 phosphorylation. The activity of JNK1 (c-Jun N-terminal kinase 1) was elevated at 2-6 h after visual exposure and was also temporally correlated to increase of endogenous P-c-Jun levels and its appearance within the AP-1 DNA-binding complex. The activities of p38 MAP kinases did not change significantly. These results demonstrate the differential engagement of MAPK signaling pathways following sensory stimulation and their relative effects upon AP-1 expression in the intact brain.
...
PMID:Rapid phosphorylation of Elk-1 transcription factor and activation of MAP kinase signal transduction pathways in response to visual stimulation. 1038 26

Cell migration and wound contraction requires assembly of actin into a functional myosin motor unit capable of generating force. However, cell migration also involves formation of actin-containing membrane ruffles. Evidence is provided that actin-myosin assembly and membrane ruffling are regulated by distinct signaling pathways in the migratory cell. Interaction of cells with extracellular matrix proteins or cytokines promote cell migration through activation of the MAP kinases ERK1 and ERK2 as well as the molecular coupling of the adaptor proteins p130CAS and c-CrkII. ERK signaling is independent of CAS/Crk coupling and regulates myosin light chain phosphorylation leading to actin-myosin assembly during cell migration and cell-mediated contraction of a collagen matrix. In contrast, membrane ruffling, but not cell contraction, requires Rac GTPase activity and the formation of a CAS/Crk complex that functions in the context of the Rac activating protein DOCK180. Thus, during cell migration ERK and CAS/Crk coupling operate as components of distinct signaling pathways that control actin assembly into myosin motors and membrane ruffles, respectively.
...
PMID:Regulation of cell contraction and membrane ruffling by distinct signals in migratory cells. 1047 63

We have examined the regulation of p21(cip1) by soluble mitogens and cell anchorage as well as the relationship between the expression of p21(cip1) and activation of the ERK subfamily of MAP kinases. We find that p21(cip1) expression in G1 phase can be divided into two discrete phases: an initial induction that requires growth factors and the activation of ERK, and then a subsequent decline that is enhanced by cell anchorage in an ERK-independent manner. In contrast to the induction of cyclin D1, the induction of p21(cip1) is mediated by transient ERK activity. Comparative studies with wild-type and p21(cip1)-null fibroblasts indicate that adhesion-dependent regulation of p21(cip1) is important for proper control of cyclin E-cdk2 activity. These data lead to a model in which mitogens and anchorage act in a parallel fashion to regulate G1 phase expression of p21(cip1). They also show that (a) growth factors and growth factor/extracellular matrix cooperation can have different roles in regulating G1 phase ERK activity and (b) both transient and sustained ERK signals have functionally significant roles in controlling cell cycle progression through G1 phase.
...
PMID:Regulation of p21(cip1) expression by growth factors and the extracellular matrix reveals a role for transient ERK activity in G1 phase. 1049 89

We have investigated the activation of the extracellular signal-regulated kinases (ERK1 and ERK2) by muscle contraction and insulin in perfused rat skeletal muscle. Both stimuli activated ERK1 and ERK2 by an upstream kinase MAP/ERK kinase (MEK)-dependent mechanism, as the MEK inhibitor PD-98059 inhibited ERK phosphorylation. The presence of the phosphatidylinositol (PI) 3-kinase inhibitors LY-294002 and wortmannin totally eradicated ERK1 and ERK2 phosphorylation in response to insulin but not contraction. Insulin and muscle contraction activated muscle glucose transport, glycogen synthase, and amino acid transport independently of ERK signaling, whereas the PI 3-kinase inhibitors abolished the stimulatory effects of insulin but not those of contraction on these three cellular processes. We conclude that 1) insulin and contraction activate ERK signaling in skeletal muscle; 2) ERK signaling is not necessary for activation of glucose and amino acid transport or glycogen synthase activity by contraction and insulin in skeletal muscle; and 3) insulin-induced activation of MEK, the upstream activator of ERK, is dependent on PI 3-kinase, whereas contraction utilizes a different mechanism.
...
PMID:Differential regulation of MAP kinase by contraction and insulin in skeletal muscle: metabolic implications. 1051 33

Vascular smooth muscle cells (VSMC) exist in either a contractile or a synthetic phenotype in vitro and in vivo. The molecular mechanisms regulating phenotypic modulation are unknown. Previous studies have suggested that the serine/threonine protein kinase mediator of nitric oxide (NO) and cyclic GMP (cGMP) signaling, the cGMP-dependent protein kinase (PKG) promotes modulation to the contractile phenotype in cultured rat aortic smooth muscle cells (RASMC). Because of the potential importance of the mitogen-activated protein kinase (MAP kinase) pathways in VSMC proliferation and phenotypic modulation, the effects of PKG expression in PKG-deficient and PKG-expressing adult RASMC on MAP kinases were examined. In PKG-expressing adult RASMC, 8-para-chlorophenylthio-cGMP activated extracellular signal- regulated kinases (ERK1/2) and c-Jun N-terminal kinase (JNK). The major effect of PKG activation was increased activation by MAP kinase kinase (MEK). The cAMP analog, 8-Br-cAMP inhibited ERK1/2 activation in PKG-deficient and PKG-expressing RASMC but had no effect on JNK activity. The effects of PKG on ERK and JNK activity were additive with those of platelet-derived growth factor (PDGF), suggesting that PKG activates MEK through a pathway not used by PDGF. The stimulatory effects of cGMP on ERK and JNK activation were also observed in low-passaged, contractile RASMC still expressing endogenous PKG, suggesting that the effects of PKG expression were not artifacts of cell transfections. These results suggest that in contractile adult RASMC, NO-cGMP signaling increases MAP kinase activity. Increased activation of these MAP kinase pathways may be one mechanism by which cGMP and PKG activation mediate c-fos induction and increased proliferation of contractile adult RASMC.
...
PMID:Activation of mitogen-activated protein kinase pathways by cyclic GMP and cyclic GMP-dependent protein kinase in contractile vascular smooth muscle cells. 1056 6

We demonstrated recently that in renal epithelial cells from collecting ducts of Madin-Darby canine kidneys (MDCK), Na(+),K(+), Cl(-) cotransport is inhibited up to 50% by ATP via its interaction with P(2Y) purinoceptors (Biochim. Biophys. Acta 1998. 1369:233-239). In the present study we examined which type of renal epithelial cells possesses the highest sensitivity of Na(+),K(+),Cl(-) cotransport to purinergic regulation. We did not observe any effect of ATP on Na(+),K(+),Cl(-) cotransport in renal epithelial cells from proximal and distal tubules, whereas in renal epithelial cells from rabbit and rat collecting ducts ATP decreased the carrier's activity by approximately 30%. ATP did not affect Na(+),K(+),Cl(-) cotransport in C7 subtype MDCK cells possessing the properties of principal cells but led to approximately 85% inhibition of this carrier in C11-MDCK cells in which intercalated cells are highly abundant. Both C7- and C11-MDCK exhibited ATP-induced IP(3) and cAMP production and transient elevation of [Ca(2+)](i). In contrast to the above-listed signaling systems, ATP-induced phosphorylation of ERK and JNK MAP kinases was observed in C11-MDCK only. Thus, our results reveal that regulation of renal Na(+),K(+),Cl(-) cotransport by P(2Y) receptors is limited to intercalated cells from collecting ducts and indicate the involvement of the MAP kinase cascade in purinergic control of this ion carrier's activity.
...
PMID:Purinergic modulation of Na(+),K(+),Cl(-) cotransport and MAP kinases is limited to C11-MDCK cells resembling intercalated cells from collecting ducts. 1056 92

Although it is established that growth factors and prostaglandins function in the maintenance of gastric mucosal integrity and in the healing of gastric mucosal injury and ulceration, the regulatory relationship between growth factors and prostaglandins in the gastric mucosa is not well characterized. Therefore, we investigated whether hepatocyte growth factor (HGF) affects expression of COX-2 (the inducible form of the prostaglandin synthesizing enzyme, cyclooxygenase) in gastric epithelial cells and whether this action is mediated through the MAP (ERK) kinase signaling pathway. In RGM1 cells (an epithelial cell line derived from normal rat gastric mucosa), HGF caused an increase in COX-2 mRNA and protein by 236% and 175%, respectively (both P<0.05). This induction of COX-2 expression was abolished by pretreatment with the MAPK kinase (MEK) inhibitor PD98059. HGF also triggered a 13-fold increase in c-Met/HGF receptor phosphorylation (P<0.005) and increased ERK2 activity by 684% (P<0.01). Pretreatment with PD98059 abolished the HGF-induced increase in ERK2 activity, but not c-Met/HGF receptor phosphorylation. The specific inhibitor of p38 MAP kinase, SB203580, had no effect on HGF-induced COX-2 expression. Thus, HGF triggers activation of the COX-2 gene in gastric epithelial cells through phosphorylation of c-Met/HGF receptor and activation of the ERK2 signaling pathway.-Jones, M. K., Sasaki, E., Halter, F., Pai, R., Nakamura, T., Arakawa, T., Kuroki, T., Tarnawski, A. S. HGF triggers activation of the COX-2 gene in rat gastric epithelial cells: action mediated through the ERK2 signaling pathway.
...
PMID:HGF triggers activation of the COX-2 gene in rat gastric epithelial cells: action mediated through the ERK2 signaling pathway. 1059 66

MAP kinases have been established to be key regulators of cellular signal transduction systems and are conserved from baker's yeast to human beings. Until now, three major types of mammalian MAP kinases (ERK, p38, and JNK/SAPK) have been reported and extensively studied. Advancement of genomic research as well as homology cloning techniques has revealed that there are several other protein kinase families that are structurally modestly related to those conventional MAP kinases. Indeed, most of them possess the TXY motif characteristic to MAP kinases in their activation loop, and can be regarded as members of the MAP kinase superfamily, yet some of them show closest overall similarity to Cdks. These kinases, all of mammalian origin, include MAK, MRK, MOK, p42KKIALRE, p56KKIAMRE, NLK, DYRK/Mnb, and Prp4. Although most of their physiological roles remain unknown, recent progress starts shedding some light on their functions.
...
PMID:Distantly related cousins of MAP kinase: biochemical properties and possible physiological functions. 1060 Apr 95

The intracellular parasite Theileria parva transforms bovine T-lymphocytes, inducing uncontrolled proliferation. Upon infection, cells cease to require antigenic stimulation and exogenous growth factors to proliferate. Earlier studies have shown that pathways triggered via stimulation of the T-cell receptor are silent in transformed cells. This is reflected by a lack of phosphorylation of key signalling molecules and the fact that proliferation is not inhibited by immunosuppressants such as cyclosporin and ascomycin that target calcineurin. This suggests that the parasite bypasses the normal T-cells activation pathways to induce proliferation. Among the MAP-kinase pathways, ERK and p38 are silent, and only Jun N-terminal kinase is activated. This appears to suffice to induce constitutive activation of the transcription factor AP-1. More recently, it could be shown that the presence of the parasite in the host cell cytoplasm also induces constitutive activation of NF-kappaB, a transcription factor involved in proliferation and protection against apoptosis. Activation is effectuated by parasite-induced degradation of IkappaBs, the cytoplasmic inhibitors which sequester NF-kappaB in the cytoplasm. NF-kappaB activation is resistant to the antioxidant N-acetyl cysteine and a range of other reagents, suggesting that activation might occur in an unorthodox manner. Studies using inhibitors and dominant negative mutants demonstrate that the parasite activates a NF-kappaB-dependent anti-apoptotic mechanism that protects the transformed cell form spontaneous apoptosis and is essential for maintaining the transformed state of the parasitised cell.
...
PMID:Interference by the intracellular parasite Theileria parva with T-cell signal transduction pathways induces transformation and protection against apoptosis. 1061 98

Sphingosine 1-phosphate (S1P) regulates cell proliferation, apoptosis, motility, and neurite retraction. Contradictory reports propose that S1P acts as either an intracellular second messenger or an extracellular ligand for cell-surface receptors. Hence, the precise signaling mechanisms mediating the diverse cellular effects of S1P remain to be determined. Here, we investigate whether S1P stimulation of cell proliferation, survival, and related signaling events can be mediated by the recently cloned Edg family members of G protein-coupled receptors. We observed that S1P treatment significantly increased proliferation of HTC4 hepatoma cells stably transfected with human S1P receptor Edg3 or Edg5, which was attributable to stimulation of cell growth and inhibition of apoptosis caused by serum starvation. Edg3 and Edg5 transduced S1P-evoked signaling events relevant to cell proliferation and survival, including activation of the ERK/MAP kinases, and immediate-early induction of c-Jun and c-Fos. Trancriptional activation of reporter genes for the c-fos promoter and the serum response element by Edg3 and Edg5 transfected in Jurkat cells was inhibited by pertussis toxin and C3 exoenzyme, implicating G(i/o)- and Rho-dependent pathways. Our data also indicated that Edg3 and Edg5 mediated the serum response element activation through transcriptional factors Elk-1 and serum response factor. Thus, specific G protein-coupled receptors Edg3 and Edg5 account for, at least in part, S1P-induced cell proliferation, survival, and related signaling events.
...
PMID:Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5. 1061 17


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

---