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

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of cultured astrocytes from 2-day-old rat cerebral hemispheres with insulin or somatomedin C (IGF1) promoted a rapid activation of a cytosolic protein kinase which phosphorylates ribosomal protein S6. Phosphorylation of substrates currently used for protein kinase assays (histone H2B and phosvitin) was not stimulated. Neither the cyclic AMP-dependent protein kinase activity nor that of protein kinase C was modified. Treatment of these astrocytes with TPA also promoted a rapid increase in S6 kinase activity in the cytosolic fraction. Simultaneously, protein kinase C disappeared from the cytosol. Neither cyclic AMP-dependent protein kinase activity nor phosvitin kinase activity was modified. The effects of insulin, IGF1 and TPA were also observed in the presence of cycloheximide. Cycloheximide also potentiated their effects. These data indicate that S6 kinase activity in astrocytes is promoted from a pre-existing molecule via the tyrosine kinase-insulin receptor and suggest that protein kinase C is implicated in the process.
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PMID:Activation of S6 kinase activity in astrocytes by insulin, somatomedin C and TPA. 353 Aug 8

A protein kinase that is stimulated from 2-10-fold by insulin and that phosphorylates ribosomal protein S6 has been characterized in 3T3-L1 cells. The detection of this activity in the 100,000 X g supernatant is facilitated by the presence of beta-glycerol phosphate or vanadate in the homogenization buffer. The activity has been purified 55-fold by chromatography on DEAE-cellulose and phosphocellulose. The resulting specific activity is 584 pmol/min/mg of protein. DEAE-cellulose chromatography followed by gel filtration on Ultrogel AcA54 or by glycerol gradient centrifugation suggests that the protein has a molecular mass of 60,000-70,000 daltons. Mg2+, and to a lesser extent Mn2+, will support phosphorylation of S6 by the activity. No proteins tested other than ribosomal protein S6 are phosphorylated. Based on its chromatographic properties and substrate specificity, the enzyme appears to be distinct from several other protein kinases that are known to phosphorylate ribosomal protein S6 in vitro. The complete characterization and purification of this enzyme may be essential to the elucidation of the mechanism of regulation of S6 phosphorylation by insulin.
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PMID:An insulin-stimulated ribosomal protein S6 kinase in 3T3-L1 cells. 353 Nov 96

A bovine liver protein serine kinase that catalyzes the multisite phosphorylation of ribosomal protein S6 has been purified to near homogeneity. The enzyme has an Mr of 67,000 on SDS-polyacrylamide gel electrophoresis and an apparent molecular weight of 55,000 on glycerol gradient sedimentation. Its enzymic properties, substrate specificity, molecular size and chromatographic behaviour are similar to those of the principal growth factor--and phorbol 12-myristate 13-acetate-stimulated S6 kinase of cultured cells.
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PMID:Purification of a bovine liver S6 kinase. 357 46

The proenzyme form of protease-activated kinase (PAK) II from reticulocytes has been shown to be activated in vitro by limited proteolysis and characterized using 40 S ribosomal subunits as substrate (T.H. Lubben and J.A. Traugh (1983) J. Biol. Chem. 258, 13992-13997). In these studies, we have shown that PAK II can be activated in a Ca2+-independent manner with phospholipids/diolein using histone 1, eukaryotic initiation factor 2, and 40 S ribosomal subunits as substrates. The addition of Ca2+ results in a diminution of PAK II activity. The Ca2+/phospholipid-dependent protein kinase (protein kinase C) is present in reticulocytes and is separated from PAK II during purification by chromatography on ADP-agarose. PAK II activated by limited proteolysis has the same substrate specificity as PAK II activated by phospholipids/diolein as shown by two-dimensional finger-printing of tryptic phosphopeptides of histone 1 and ribosomal protein S6, indicating proteolysis did not alter the specificity of the enzyme. Lipid vesicles decrease the Km of PAK II for histone 1 by 10-fold, while no effect is observed on the Km or the Vmax of PAK II for ATP. These results are strikingly different from the kinetics reported for protein kinase C, where the activators increase the Vmax for ATP. The two enzymes have similar, if not identical, substrate specificity with histone 1, as determined by phosphopeptide mapping, but at least 8-fold more protein kinase C than PAK II is required to incorporate a comparable amount of phosphate into S6 and it is not possible to incorporate stoichiometric amounts of phosphate into S6 with protein kinase C. The two protein kinases also differentially phosphorylate other substrates. The data support the hypothesis that PAK II and protein kinase C are closely related, but unique enzymes.
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PMID:Ca2+-independent activation of protease-activated kinase II by phospholipids/diolein and comparison with the Ca2+/phospholipid-dependent protein kinase. 377 73

The effects of phosphorylation of ribosomal protein S6 by two different protein kinases, the cAMP-dependent protein kinase and the mitogen-stimulated S6 kinase, or translation of globin mRNA in a reconstituted system and on binding of globin mRNA to 40 S ribosomal subunits were examined. The cAMP-dependent protein kinase incorporated 1.5 mol of phosphate/mol of 40 S ribosomal subunits. Phosphorylation of S6 by the cAMP-dependent protein kinase had no effect on binding of 3' terminus-labeled globin mRNA to 40 S ribosomal subunits. [3H]Leucine incorporation with 40 S ribosomal subunits phosphorylated by the cAMP-dependent protein kinase was identical to that observed with nonphosphorylated 40 S ribosomal subunits, although on occasion, a slight inhibition (less than 10%) was observed; there was no effect on the rate of synthesis of either the alpha or beta chains of globin. Phosphorylation with the mitogen-stimulated S6 kinase (2.5 mol/mol) did not alter binding of globin mRNA to 40 S ribosomal subunits; however, translation of globin mRNA in the reconstituted protein-synthesizing system was stimulated up to 4-fold over that observed with nonphosphorylated subunits. Synthesis of both the alpha and beta chains of globin was enhanced by phosphorylation as shown by electrophoretic analysis. Since the sites phosphorylated by the mitogen-stimulated S6 kinase are identical to those observed in vivo in response to insulin and growth-promoting compounds, the data support the hypothesis that enhanced synthesis of specific proteins may be due to phosphorylation of S6 and that differential phosphorylation of S6 can alter translation of natural mRNA.
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PMID:Phosphorylation of ribosomal protein S6 by cAMP-dependent protein kinase and mitogen-stimulated S6 kinase differentially alters translation of globin mRNA. 381 53

A protein kinase specific for ribosomal protein S6 has been purified from eggs of Xenopus laevis. As visualized on a silver-stained polyacrylamide gel, the major protein in the preparation migrated with a Mr of 90,000. Incubation of the enzyme preparation with [gamma-32P]ATP led to phosphorylation of this protein on serine residues. Upon glycerol gradient centrifugation, the S6 kinase activity and the Mr 90,000 protein both sedimented with a Mr of 50,000-55,000. Two-dimensional gel electrophoresis demonstrated that up to 4-5 phosphate groups per S6 molecule could be incorporated with this enzyme in vitro, and two-dimensional peptide mapping demonstrated that the phosphopeptides from S6 labeled in vitro with the enzyme comigrated with those from highly phosphorylated S6 labeled in vivo in response to progesterone treatment. The purified S6 protein kinase did not phosphorylate at a significant rate ribosomal protein S10, histone H1, histone H4, mixed histones, casein, or phosvitin, indicating a high degree of substrate specificity. These results indicate that activation of a single S6 protein kinase may be sufficient to account for increased S6 phosphorylation after a growth stimulus.
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PMID:A protein kinase from Xenopus eggs specific for ribosomal protein S6. 385 26

Epidermal growth factor stimulates phosphorylation of ribosomal protein S6 in serum-starved Swiss 3T3 cells, leading to the formation of highly phosphorylated derivatives containing 4-5 phosphates. Two-dimensional analysis of tryptic phosphopeptides of S6 shows an identical pattern to the ones obtained previously in other cells in response to insulin and the tumor promoting phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate. This suggests a common intracellular mediator of S6 phosphorylation by different growth promoting agents. It is proposed that the potential mediator of this phosphorylation is the Ca2+-independent, cAMP-independent protein kinase, protease activated kinase II, as shown by the extent of phosphorylation and the tryptic phosphopeptide maps of S6 with highly purified enzyme [(1983) J. Biol. Chem. 258, 13998-14002].
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PMID:Protease-activated kinase II as the mediator of epidermal growth factor-stimulated phosphorylation of ribosomal protein S6. 388 23

Treatment of 3T3-L1 cells with 0.1-1.0 nM insulin results in rapid (5-15 min) activation of a soluble protein kinase that phosphorylates serine residues in ribosomal protein S6. The insulin-stimulated kinase activity is detectable in confluent, nongrowing preadipocytes and adipocytes. In the presence of 2 micrograms of cycloheximide per ml, preconfluent 3T3-L1 cells also respond to insulin by acquiring an S6 kinase activity whose properties are the same as those of the enzyme activity elicited by insulin alone in growth-inhibited cells. The principal insulin-stimulated S6 kinase has a Mr of approximately equal to 50,000-60,000; there is a variable amount of activity that sediments with a Mr of about 80,000. The soluble enzyme exhibits optimal activity between pH 8 and pH 9, requires Mg2+ (10-20 mM), and is inhibited by Ca2+ (0.5 mM), Mn2+ (0.05 mM), and NaF (30 mM). GTP cannot substitute for ATP in the phosphotransferase reaction; cAMP, cGMP, phosphatidylserine plus diolein, the cAMP-dependent protein kinase inhibitor, and heparin (0.7 micrograms/ml) are without effect. Although treatment of 3T3-L1 cells with insulin does not influence the activity or the subcellular distribution of the phospholipid and Ca2+-dependent protein kinase C, exposure to the phorbol tumor promoter phorbol 12-myristate 13-acetate (PMA) results in translocation of protein kinase C to the membrane and activation of a soluble phospholipid and Ca2+-independent S6 protein kinase that has the same magnitude of activity and sedimentation behavior as the insulin-induced activity. Trypsin treatment of either 3T3-L1 cytosolic extracts or partially purified 3T3-L1 protein kinase C generates a small amount of S6 kinase activity of Mr 50,000. This activity, resolved by sucrose gradient centrifugation, is less active than that elicited by either insulin or PMA and, unlike the activities generated by insulin and PMA, is associated with histone kinase activity. The data suggest that the S6 kinase elicited by either insulin or PMA is neither protein kinase C, its phospholipid, and Ca2+-independent proteolytic derivative nor the result of proteolytic activation of an inactive proenzyme that can be reproduced by trypsin treatment of cell extracts in vitro.
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PMID:Activation of S6 kinase activity in 3T3-L1 cells by insulin and phorbol ester. 389 33

Phosphorylation of ribosomal protein S6 in NIH 3T3 fibroblasts is dependent on the presence of serum, but after transformation of these cells by Abelson murine leukemia virus (Ab-MuLV), S6 remained highly phosphorylated on serine residues either in the absence or the presence of serum. To investigate whether S6 phosphorylation in this system was a consequence of the action of the Ab-MuLV tyrosine-specific protein kinase, purified Ab-MuLV kinase made in Escherichia coli was microinjected into Xenopus oocytes and was observed to cause a 7- to 15-fold increase in the phosphorylation of S6 on serine residues. Two-dimensional phosphopeptide maps of S6 phosphorylated in Ab-MuLV-transformed NIH cells in the absence of serum were identical to those of S6 isolated from normal cells grown in the presence of serum. In addition, S6 from oocytes injected with Ab-MuLV kinase yielded an S6 phosphopeptide map indistinguishable from that of serum-stimulated NIH 3T3 cells, whereas S6 from control oocytes lacked several phosphopeptides. Ab-MuLV kinase did not phosphorylate S6 directly in vitro, and microinjection of a mutant Ab-MuLV protein lacking kinase activity had no effect. These results indicate that the Ab-MuLV kinase interacts with a cellular pathway to enhance S6 phosphorylation by directly or indirectly activating an S6 protein kinase and/or inactivating an S6 protein phosphatase.
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PMID:Phosphorylation of ribosomal protein S6 on serine after microinjection of the Abelson murine leukemia virus tyrosine-specific protein kinase into Xenopus oocytes. 391 7

Protein kinase capable of phosphorylating 40S ribosomal protein S6 on serine residues has been detected in chicken embryo fibroblasts. This activity appears to be regulated in direct response to expression of pp60v-src in chicken embryo fibroblasts infected with a temperature-sensitive transformation mutant of Rous sarcoma virus. Partially purified S6 kinase was highly specific for S6 in 40S ribosomal subunits. The S6 kinase was not inhibited by calcium or by the heat-stable inhibitor of cAMP-dependent protein kinase, nor was it activated by phosphatidylserine, diacylglycerol, and calcium. Thus, it is distinct from protein kinase C and cAMP-dependent protein kinase, which are capable of phosphorylating S6 in vitro. The tumor-promoter phorbol 12-myristate 13-acetate also stimulated ribosomal protein S6 kinase activity in serum-starved chicken embryo fibroblasts, whereas phorbol, the inactive analog of phorbol 12-myristate 13-acetate, had no effect. S6 kinase activity stimulated by expression of pp60v-src, by phorbol 12-myristate 13-acetate, or by serum growth factors exhibited similar chromatographic properties upon ion-exchange chromatography. These results suggest that a common protein kinase may be activated by three diverse stimuli all involved in regulating cell proliferation.
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PMID:Regulation of a ribosomal protein S6 kinase activity by the Rous sarcoma virus transforming protein, serum, or phorbol ester. 393 63


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