Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.1 (myosin ATPase)
 1,140 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both protein kinase C (PKC) and extracellular signal-regulated kinases (ERK1/2) are involved in mediating vascular smooth muscle contraction. We tested the hypotheses that in addition to PKC activation of ERK1/2, by negative feedback ERKs modulate PKC-induced contraction, and that their interactions modulate both thick and thin myofilament pathways. In ovine middle cerebral arteries (MCA), we measured isometric tension and intracellular free calcium concentration ([Ca(2+)](i)) responses to PKC stimulation [phorbol 12,13-dibutyrate (PDBu), 3 x 10(-6) M] in the absence or presence of ERK1/2 inhibition (U-0126, 10(-5) M). After PDBu +/- ERK1/2 inhibition, we also examined by Western immunoblot the levels of total and phosphorylated ERK1/2, caldesmon(Ser789), myosin light chain(20) (MLC(20)), and CPI-17. PDBu induced significant increase in tension in the absence of increased [Ca(2+)](i). PDBu also increased phosphorylated ERK1/2 levels, a response blocked by U-0126. In turn, U-0126 augmented PDBu-induced contractions. PDBu also was associated with significant increases in phosphorylated caldesmon(Ser789) and MLC(20) levels, each of which peaked at 5 to 10 min. PDBu also increased phosphorylated CPI-17 levels, which peaked at 2 to 3 min. Rho kinase inhibition (Y-27632, 3 x 10(-7) M) did not alter PDBu-induced contraction. These results support the idea that PKC activation can increase CPI-17 phosphorylation to decrease myosin light chain phosphatase activity. In turn, this increases MLC(20) phosphorylation in the thick filament pathway and increases Ca(2+) sensitivity. In addition, ERK1/2-dependent phosphorylation of caldesmon(Ser789) was not necessary for PDBu-induced contraction and appears not to be involved in the reversal of caldesmon's inhibitory effect on actin-myosin ATPase.
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PMID:PKC-induced ERK1/2 interactions and downstream effectors in ovine cerebral arteries. 1595 60

Investigations of actin function during the cell cycle have focused primarily on cytokinesis. Here, we describe the role of actin at the entry into mitosis in primary mammalian cells. Depolymerization of actin with cytochalasin D or inhibition of myosin ATPase with butanedione-2-monoxime (BDM) at G(2) blocked the mitotic spindle formation and central positioning of the nucleus in synchronized MEF and IMR90 cells. Time-lapse microscopy confirmed that these treatments inhibit both spindle formation and separation of duplicated centrosomes to the opposite poles. Concurrent with actin dysfunction, activation of Cdc2 and nuclear localization of cyclin B1 were delayed. Furthermore, cyclin A degradation that is necessary for nuclear envelope breakdown (NEBD) in early mitosis was deferred, supporting the conclusion that mitotic onset was delayed. The activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) was sustained in these cells, and the use of a specific ERK inhibitor or a dominant negative form of ERK2 abrogated this delay of entry into mitosis. This delay of mitotic entry and the sustained ERK1/2 activity by actin dysfunction was observed only in primary cells and not in transformed cancer cell lines. These observations demonstrate that an intact actin cytoskeleton is necessary for entry into mitosis and that ERK1/2 is involved in monitoring actin dysfunction to control the onset of mitosis, suggesting the presence of an actin checkpoint at the G(2)/M transition in primary mammalian cells.
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PMID:Actin dysfunction activates ERK1/2 and delays entry into mitosis in mammalian cells. 1758 24

The molecular mechanisms by which resistance exercise enlarges muscle mass, particularly the mass of fast-twitch type II fibers, are likely to involve enhanced phosphorylation/activation of key enzymes regulating protein synthesis. The hypothesis is that resistance exercise influences the phosphorylation of such key signaling proteins to a greater extent in type II than in type I fibers. Six recreationally active male subjects performed four sets of six maximal lengthening contractions with one leg. Muscle biopsies were taken from the vastus lateralis before and immediately after exercise and following 1 and 2 h of recovery. Samples were freeze-dried, and individual muscle fibers were dissected out and identified as type I or type II after staining for myosin ATPase. Phosphorylation of p70(S6k) on Thr(389) and S6 in type II fibers was increased three-to fourfold and six- to ninefold (P < 0.05), respectively, 1 and 2 h after exercise, whereas phosphorylation in type I fibers remained unchanged. Phosphorylation of Akt, mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) was unaltered in both fiber types, whereas that of eukaryotic elongation factor 2 (eEF2) was attenuated 20-45% (P < 0.05) in type II fibers during recovery. Phosphorylation of ERK1/2 was elevated six- to sevenfold (P < 0.05) immediately after exercise, and p38 MAPK phosphorylation was increased three- to fourfold (P < 0.05) for as long as 1 h after exercise in both types of fibers, although the level was markedly higher in type II fibers (P < 0.05). In conclusion, the elevation of p70(S6k) and the reduction of eEF2 phosphorylation in the type II fibers following resistance exercise suggest stimulation of protein synthesis, which may contribute to a more pronounced enlargement of these fibers. Our findings also suggest that p70(S6k) is activated, at least in part, via pathways not involving Akt-mTOR and MAPK.
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PMID:Maximal lengthening contractions induce different signaling responses in the type I and type II fibers of human skeletal muscle. 1911 58