Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously reported that both hypoxia and hypoxia followed by reoxygenation (hypoxia/reoxygenation) rapidly and sequentially activate mitogen-activated protein kinase kinase kinase (MAPKKK) activity of Raf-1. This was followed by the sequential activation of MAP kinase kinase (MAPKK). MAP kinases (p42mopk and p44mopk), and S6 kinase (p90rsk). In this study, we demonstrated that both hypoxia and hypoxia/ reoxygenation caused rapid activation of Src family tyrosine kinases, p60c-src and p59c-fyn, which are upstream mediators of MAP kinase activation. This was followed by the activation of p21ras. Because Src family tyrosine kinases are known to be cell-surface-associated kinases and upstream regulators of p21ras, these results strongly suggested that activation of Src family tyrosine kinases plays a key role in triggering intracellular signaling cascades in cardiac myocytes in response to hypoxia and hypoxia/reoxygenation.
Biochem Biophys Res Commun 1996 Sep 13
PMID:Hypoxia and hypoxia/reoxygenation activate Src family tyrosine kinases and p21ras in cultured rat cardiac myocytes. 880 68

Externally regulated phosphatase (ERP or MKP-1) is a dual specificity phosphatase that has been implicated in the dephosphorylation of mitogen activated protein kinases (MAP kinases). MAP kinase is activated in response to external signals and in turn phosphorylates proteins essential to the regulation of cell growth. To study the role of ERP/MKP-1 protein in mammalian development and its function in signal transduction we have generated mice, embryonic stem (ES), cells and mouse embryo fibroblasts (MEFs) that are deficient in the ERP/MKP-1 protein. ERP/MKP-1-deficient mice are born at normal frequency, are fertile and present no phenotypic or histologic abnormalities. MAP kinase activity and the induction of c-fos mRNA is unaltered in MEFs lacking the ERP/MKP-1 protein, indicating no alteration of the MAP kinase pathway. In addition, ERP/MKP-1 deficient MEFs grow and enter DNA synthesis at the same rate as control cells. Our results demonstrate that the activity of ERP/MKP-1 is not essential for embryo development and indicate that the lack of ERP/MKP-1 activity can be compensated by other phosphatases in vivo.
Oncogene 1996 Sep 05
PMID:Disruption of the erp/mkp-1 gene does not affect mouse development: normal MAP kinase activity in ERP/MKP-1-deficient fibroblasts. 880 81

Simian virus 40 (SV40) binding to growth-arrested cells activated an intracellular signalling pathway that induced the up-regulation of the primary response genes c-myc, c-jun and c-sis within 30 min and of JE within 90 min. The up-regulation of the primary response genes occurred in the presence of cycloheximide and when UV-inactivated SV40 was adsorbed to cells. SV40 binding did not activate Raf or mitogen-activated protein kinase (MAP/ERK1), or mobilize intracellular Ca2+. The SV40-induced up-regulation of c-myc and c-jun was blocked by the tyrosine kinase inhibitor, genistein, and by the protein kinase C (PKC) inhibitor, calphostin C, but not by expression of the MAP kinase-specific phosphatase, MKP-1. These results suggest that the SV40-induced signalling pathway includes the activities of a tyrosine kinase and a Ca(2+)-independent isoform of PKC, but not of Raf or MAP kinase. Finally, SV40 infectious entry into cells was specifically and reversibly blocked by genistein.
J Gen Virol 1996 Sep
PMID:Extracellular simian virus 40 induces an ERK/MAP kinase-independent signalling pathway that activates primary response genes and promotes virus entry. 881 Oct 17

Near-infrared spectrophotometry-determined cerebral (ScO2) and muscle oxygen saturations (SmO2) were followed in 15 volunteers during passive 50 degrees head-up-tilt-induced central hypovolaemia, and in nine volunteers during ventilatory manoeuvres affecting arterial carbon dioxide tension. During head-up tilt, mean arterial pressure [MAP, 88 (77-118) to 97 (80-136) mmHg, median and range] and heart rate [HR; 66 (49-77) to 87 (42-132) beats min-1 P < 0.01] increased, but after 22 (1-45) min they declined [to 61 (40-91) mmHg and 69 (38-109) beats min-1, respectively, P = 0.001] and pre-syncopal symptoms developed. Central hypovolaemia was indicated by an increased thoracic electrical impedance, and a decreased cardiac output and central venous oxygen saturation. The arterial oxygen saturation, pulmonal oxygen uptake and skin temperatures remained constant. The ScO2 remained stable at 72 (62-77)% until the pre-syncopal incidence, when it decreased to 62 (31-73)% (P = 0.001), and tilt down made it increase to 75 (36-87)% (P < 0.05) before the recovery value was established. In contrast, SmO2 decreased during tilting [75(70-87) to 65 (53-70)%], and recovered to 70 (53-83)%, P < 0.01) during the hypotensive episode. The end-tidal CO2 tension decreased only during tilt-up. The ScO2 decreased, and SmO2 increased during hyperventilation, and ScO2 increased during breathing of 5% carbon dioxide. Rebreathing from a bag made SmO2 decrease and resulted in a biphasic ScO2 response: it first increased and subsequently decreased. Cardiovascular changes during tilt were not reflected in skin temperature. The ScO2 reflected the maintained autoregulation of cerebral blood flow until the perfusion pressure decreased markedly. In contrast, SmO2 mirrored muscle vasoconstriction early during tilt, and vasodilatation when pre-syncopal symptoms appeared.
Clin Physiol 1995 Sep
PMID:Brain and muscle oxygen saturation during head-up-tilt-induced central hypovolaemia in humans. 884 72

It is well accepted that sympathetic tone is elevated in chronic heart failure (HF) and that the cardiac sympathetic afferent reflex is a sympathoexcitatory reflex. There have been no studies designed to examine the role of this reflex in control of sympathetic outflow in the HF state. In this study we tested the hypothesis that cardiac sympathetic afferent reflexes are enhanced in HF and are, therefore, capable of contributing to the increase in sympathetic outflow in this disease state. Ventricular pacing was carried out in 14 dogs until signs of HF were evident. Fourteen sham dogs served as controls. At the time of the acute experiment the dogs were anesthetized with alpha-chloralose. The hemodynamic [arterial pressure and heart rate (HR)] and renal sympathetic nerve activity (RSNA) responses to left ventricular epicardial application of two doses of bradykinin (BK) and capsaicin (Cap) were determined in the sinoaortic-denervated and vagotomized state. The MAP, RSNA, and HR responses to BK were greater in the HF group compared with the sham group. The RSNA response to BK (50 micrograms) in the HF group was significantly increased (34.0 +/- 5.9 vs. 11.5 +/- 4.2%, P < 0.05). The MAP, RSNA, and HR responses to Cap in the HF group were similar to the responses to BK. The RSNA response to Cap in the HF group was significantly increased (29.8 +/- 11.3 vs. 13.8 +/- 2.3% for 10 micrograms, P < 0.05 and 46.5 +/- 10.7 vs. 18.7 +/- 3.1% for 100 micrograms, P < 0.05). The cyclooxygenase blocker indomethacin (5 mg/kg i.v.) attenuated the reflex responses to BK in the HF group. These data suggest that the enhanced cardiac sympathetic afferent reflex to epicardial BK in HF appears to be mediated by altered levels of prostaglandin synthesis. Blockade of cardiac sympathetic afferents with topical lidocaine reduced baseline of RSNA significantly more in the HF state than in the normal state (-24.2 +/- 3.6 vs. -4.3 +/- 4.5%, P < 0.05). We conclude from these data that the cardiac sympathetic afferent reflex is sensitized in the HF state and speculate that this enhanced cardiac sympathetic afferent reflex may contribute to the sustained higher sympathetic tone in chronic HF.
Am J Physiol 1996 Sep
PMID:Cardiac sympathetic afferent reflex in dogs with congestive heart failure. 885

Basic fibroblast growth factor (bFGF) is a potent mitogen for bone. In this study, we utilized the clonal rat osteoblastic cell line, Py1a, to examine signal transduction by bFGF and to determine the role of mitogen activated protein kinases (MAPK) and induction of c-fos mRNA in the mitogenic response to bFGF. Stimulation of [3H]thymidine incorporation (TDR) into DNA by bFGF was determined in the presence of phorbol myristate acetate of (PMA) to down-regulate the protein kinase C (PKC) pathway, genistein, an inhibitor of tyrosine kinase and H-7, a PKC inhibitor, bFGF 10(-8) M and PMA 10(-7) M increased TDR by 242 and 245%, respectively. Treatment with bFGF or PMA for 5 or 30 minutes increased tyrosine phosphorylation of multiple proteins, and immunoblotting with MAPK-specific antibody revealed that two of these bands were the 42 and 44 kD isoforms of MAPK. PMA and bFGF induced c-fos mRNA expression at 30 minutes. Genistein at 10 micrograms/ml blocked the mitogenic effect of bFGF and partially inhibited the mitogenic effect of PMA. Genistein at 100 micrograms/ml also blocked both bFGF- and PMA-induced increases in c-fos mRNA. A 24 h pretreatment with PMA at 10(-7) M inhibited the mitogenic response, tyrosine phosphorylation of MAPK, and induction of c-fos mRNA subsequent to the addition of PMA, but not bFGF. H-7 at 50 microM blocked bFGF-induced mitogenesis and c-fos induction, but did not inhibit bFGF-induced tyrosine phosphorylation of MAPK. In this study, we show that the signaling pathway of bFGF and PMA are similar in that they both induce tyrosine phosphorylation of MAP kinases and activate c-fos. However, the signaling pathways ultimately diverge in that once the PKC pathway is down-regulated by PMA pretreatment or blocked by the PKC inhibitor H-7, tyrosine phosphorylation of MAP kinase, c-fos induction, and the mitogenic effect of PMA is blocked. In contrast, down-regulation of the PKC pathway inhibits c-fos and the mitogenic response to bFGF, but not bFGF's effects on tyrosine phosphorylation of MAP kinase.
J Bone Miner Res 1996 Sep
PMID:Signal transduction by basic fibroblast growth factor in rat osteoblastic Py1a cells. 886

This study examined the effects of administering 0.5, 4, 10, and 30 mL/kg of Diaspirin Crosslinked Hemoglobin (DCLHb) in a swine model of non-lethal hemorrhagic shock. Thirty unanesthetized animals were bled (30 mL/kg, 1 mL/kg/min) and either recovered without treatment (Untreated Control, UC) or infused with 10 g/dL DCLHb (0.5, 4.0, 10 or 30 mL/kg at 1 mL/kg/min) or Lactated Ringer (LR, 90 mL/kg at 3 mL/kg/min). DCLHb caused dose-related increases in MAP. Both the 10 and 30 mL/kg doses of DCLHb increased MAP more than UC or LR. Lower doses of DCLHb and LR had effects on MAP similar to UC. After hemorrhage, CO increased in all groups. The effect of DCLHb on CO was dose-related. Only LR and 30 mL/kg of DCLHb transiently (through 90 min) increased CO more than UC. CO in animals given lower doses of DCLHb was comparable to UC. DCLHb (10 and 30 mL/kg) improved base excess and lactate concentrations, two indices of global perfusion, more rapidly and to a greater extent than either UC or LR. In this swine model of hemorrhage, even small doses of DCLHb exerted measurable beneficial effects on blood pressure and perfusion.
Artif Cells Blood Substit Immobil Biotechnol 1996 Sep
PMID:Resuscitation with increasing doses of diaspirin crosslinked hemoglobin in swine. 887 22

The immediate early gene-encoded enzyme, MAP kinase phosphatase 1 (MKP-1), is thought to be a key element in controlling cellular signalling pathways activated by MAP kinases. Since MAP kinase have been demonstrated to participate in neuronal stimulus-transcription coupling following seizure activity, the present study investigated the induction of MKP-1 in the rat brain after limbic epilepsy. MKP-1 expression was studied with a polyclonal antiserum by Western blots, immunocytochemistry and immuno-electron microscopy at different time periods between 1 and 24 h after kainic acid-induced limbic seizures. MKP-1 induction was identified in dentate granule cells of the hippocampus but not in pyramidal neurons, furthermore in neurons of the outer layers of the neocortex, as well as in neurons of the lateral nucleus of the bed of the stria terminalis. Immuno-electron microscopy demonstrated that MKP-1 was localized in the neuronal nucleus, where the substrate of MKP-1, activated MAP kinases, are also found. In view of the restricted areas of MKP-1 expression and the widespread areas of altered MAP kinases activity it can be concluded that in the majority of CNS populations other mechanisms than MKP-1 induction are responsible for the shut-off of MAP kinases following seizure activity. MKP-1 may contribute in the specific subpopulations where it is induced to the post-translational control of inducible transcription factors of the fos, jun and myc family.
Brain Res Mol Brain Res 1996 Sep 05
PMID:Transient expression of the mitogen-activated protein kinase phosphatase MKP-1 (3CH134/ERP1) in the rat brain after limbic epilepsy. 888 36

To test the hypothesis that brain injury impairs control of vascular tone during compensation from hemorrhagic shock, Sprague-Dawley rats underwent fluid-percussion brain injury (or sham injury control) followed by a stepwise hemorrhage period to 1/2 baseline mean arterial pressure (1/2 MAP), a shock period holding at 1/2 MAP for 30 min, and a resuscitation period. Aortic blood flow (ABF) was measured and vascular conductance (ABF/MAP) was calculated. No differences occurred between groups during the stepwise hemorrhage period. During the 30 min shock period, controls decreased conductance from .2 +/- .07 to .16 +/- .04 and required repeated additional hemorrhage (3.4 +/- 1.3 cc) to maintain 1/2 MAP. In contrast, brain-injured animals increased conductance from .21 +/- .07 to .24 +/- .06 (p < .05) during the shock period and required repeated fluid replacements (3.0 +/- 1.3 cc lactated Ringer's (LR), p < .05) to maintain 1/2 MAP. Following resuscitation, conductance appropriately increased to .31 +/- .05 in controls but did not change (.25 +/- .04, p < .05) in brain-injured animals. We conclude that brain injury adversely affects control of vascular tone during shock and resuscitation in this model.
Shock 1996 Sep
PMID:Fluid-percussion brain injury adversely affects control of vascular tone during hemorrhagic shock. 888 88

Cell morphogenesis is a fundamental phenomenon that involves understanding a number of biological processes including the developmental program, polarity and cell division. Fission yeast sts5 mutant cells are round rather than cylindrical with cortical actin randomly dispersed. Genetic analyses demonstrate that the sts5+ gene is required for maintenance of cell shape during interphase when the cell normally exhibits polarised growth. The sts5 mutant is not defective in cell wall integrity. Deletion of ppe1+, which encodes a type 2A-like protein phosphatase, shows similar phenotypes to the sts5 mutant and these two mutations are synthetically lethal. Multicopy plasmids containing either the protein kinase C-like gene pck1+ or the protein tyrosine phosphatase pyp1+, an inhibitor of an osmosensing Sty1/Spc1 MAP-kinase, are capable of suppressing the sts5 mutation. Consistent with this, we have found that the wis1 mutation, which is defective in a MAP-kinase kinase of the pathway, suppresses the sts5 mutation. The predicted sts5+ gene product exhibits sequence similarity to two yeast proteins, Dis3 and Ssd1 and a nematode protein, F46E8.6, where the former two yeast proteins have been shown to be involved in cell cycle control and cell morphogenesis. The sts5+ gene is not essential for cell viability, but is absolutely required for polarised growth as the gene disruption showed the same phenotypes as those of the original mutants. Overexpression of the sts5+ gene resulted in altered cell morphology and, cortical actin in these overproducing cells was also abnormal, fainter and often dispersed. Anti-Sts5 antibody specifically detected a 130 kDa protein by western blotting. A green fluorescent protein-Sts5 fusion protein localised in the cytoplasm with a discrete punctate pattern, suggesting that the Sts5 protein is a component of a novel structure. These results have indicated that the Sts5 protein is a crucial determinant of polarised growth and that it functionally interacts with the serine/threonine phosphatase, protein kinase C, and an osmosensing MAP-kinase to maintain cell morphology.
J Cell Sci 1996 Sep
PMID:The fission yeast sts5+ gene is required for maintenance of growth polarity and functionally interacts with protein kinase C and an osmosensing MAP-kinase pathway. 888 83


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