Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.26 (GSK)
 6,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant p90rsk expressed from baculovirus was found to be phosphorylated and activated by glycogen synthase kinase-3 (GSK-3) in vitro. Phosphorylation of p90rsk by both GSK-3 alpha and GSK-3 beta isoforms was predominantly on threonine residues. Activated p90rsk, resulting from co-expression in insect cells with the oncogenic protein tyrosine kinase p60v-src, was able to phosphorylate GSK-3 but was a poor GSK-3 substrate. These results suggest a potentially novel regulatory connection in the signal transduction cascades in which p90rsk participates.
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PMID:Phosphorylation and activation of p90rsk by glycogen synthase kinase-3. 769 38

We report here the isolation of the Arabidopsis thaliana gene AtK-1. The predicted protein sequence of AtK-1 shows 70% identity to the Arabidopsis ASK and alfalfa MsK kinases that are homologs of the Drosophila shaggy and rat GSK-3 serine/threonine protein kinases playing an important role in signal transduction processes in animals. Northern analysis of different organs revealed exclusive expression in inflorescences suggesting an involvement of the AtK-1 kinase in reproduction-specific processes.
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PMID:Inflorescence-specific expression of AtK-1, a novel Arabidopsis thaliana homologue of shaggy/glycogen synthase kinase-3. 786 93

To identify consensus sequence motif for a new family of protein kinase termed autophosphorylation-dependent protein serine/threonine kinase (auto-kinase), we have tested several synthetic peptides. The well established protein serine/threonine kinases such as cAMP-dependent protein kinase, Ca2+/calmodulin-dependent protein kinase (CaM-kinase), and protein kinase C were found to be inactive toward phosphorylation of syntide-3 (RPRPASVPPSPSLSRHA), which turned out to be an excellent substrate only for auto-kinase, indicating that syntide-3 is a specific substrate for auto-kinase. Modification of syntide-3 to become RPRPASVPPS/T did not affect the activity of auto-kinase. By contrast, autokinase became rather or almost inactive when the peptide was modified to become RPRPASVPPA/G/F/K/R/D/E/Y, indicating that amino acid number 10 in syntide-3 is crucial to the sequence motif recognized by auto-kinase. Phosphorylation of myelin basic protein (MBP) by autokinase revealed that auto-kinase predominantly phosphorylates MBP on one particular site with RT-T(p)HYGS as the phosphorylation site sequence, which could not be phosphorylated by any other reported MBP kinases including cAMP-dependent protein kinase, CaM-kinase, protein kinase C, mitogen-activated protein kinase, and kinase FA/GSK-3. Taken together, the results provide initial evidence that -Arg-X-(X)-Ser/Thr-X3-Ser/Thr- may represent a unique consensus sequence motif specifically recognized by autophosphorylation-dependent protein kinase, a new family of multi-substrate/multifunctional protein serine/threonine kinase.
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PMID:Identification of -R-X-(X)-S/T-X3-S/T- as consensus sequence motif for autophosphorylation-dependent protein kinase. 785 32

We report here the sequence of RPK1 (for Regulatory cell Proliferation Kinase), a new Saccharomyces cerevisiae gene coding for a protein with sequence similarities to serine/threonine protein kinases. The protein sequence of 764 amino acids includes an amino-terminal domain (residues 1-410), which may be involved in regulation of the kinase domain (residues 411-764). The catalytic domain of Rpk1 is not closely related to other known yeast protein kinases but exhibits strong homology to a newly discovered group of mammalian kinases (PYT, TTK, esk) with serine/threonine/tyrosine kinase activity. Null alleles of RPK1 are lethal and thus this gene belongs to the small group of yeast protein kinase genes that are essential for cell growth. In addition, eliminating the expression of RPK1 gives rise to the accumulation of non-viable cells with less than a 1 N DNA content suggesting that cells proceed into mitosis without completion of DNA synthesis. Therefore, the Rpk1 kinase may function in a checkpoint control which couples DNA replication to mitosis. The level of the RPK1 transcript is extremely low and constant throughout the mitotic cycle. However it is regulated during cellular differentiation, being decreased in alpha-factor-treated a cells and increased late in meiosis in a/alpha diploids. Taken together, our results suggest that Rpk1 is involved in a pathway that coordinates cell proliferation and differentiation.
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PMID:RPK1, an essential yeast protein kinase involved in the regulation of the onset of mitosis, shows homology to mammalian dual-specificity kinases. 802 80

We have recently isolated the cDNA for a unique human 97-kDa kinase, TTK, by expression screening of a cDNA expression library using anti-phosphotyrosine antibodies. When expressed in Escherichia coli, TTK can phosphorylate serine, threonine, and tyrosine residues. Thus TTK appears to belong to a newly described family of kinases able to phosphorylate all three hydroxy amino acids. This family of multispecific kinases includes several other kinases involved in cell cycle progression. In support of a possible role in regulating cell cycle progression, TTK message is readily detected in rapidly proliferating tissues in vivo including testes, thymus, bone marrow, and many malignant tumors, but not in benign tissues with a low proliferative rate in vivo. To determine the effect of cell activation and cell cycle progression on TTK expression, we measured TTK mRNA and protein levels as well as kinase activity in freshly isolated T cells or IL-2-expanded T cell blasts activated to proliferate by the addition of a variety of mitogens. TTK mRNA levels, protein levels, and kinase activity were greatly enhanced when either freshly isolated PBL or T cell blasts were activated by cross-linking the TCR complex by mitogenic lectins or by bypassing the TCR with phorbol esters and cation ionophores. Incubation with IL-2 increased TTK expression in PBL blasts, which proliferate in response to IL-2, but not in fresh PBL, which do not proliferate in response to IL-2. TTK expression was blocked by either cyclosporin A or FK520, which inhibit IL-2 production and could be recovered by the addition of exogenous IL-2. Furthermore, TTK expression was prevented by incubation of the cells with rapamycin, which blocks IL-2 signaling. Thus, TTK expression in T cells appears to be a consequence of IL2-induced cell proliferation. Agonist-induced TTK expression was a delayed event occurring 12 to 24 h after activation of PBL blasts and 48 to 72 h after activation of fresh PBL. TTK protein and mRNA expression increased in both fresh PBL and T cell blasts concurrently with passage of cells through S phase as indicated by [3H]TdR incorporation and cell cycle analysis of propidium iodide-stained cells. TTK mRNA and protein levels reached a maximum as cells entered the G2 phase of the cell cycle. These results were confirmed by cell cycle blockade studies with aphidicolin and nocodazole wherein TTK protein levels are not detected in cells in G1 and are readily detectable in cells in the S and G2 phases of the cell cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:IL-2-induced expression of TTK, a serine, threonine, tyrosine kinase, correlates with cell cycle progression. 825 11

During neurogenesis in Drosophila, groups of equipotential, neurally competent cells choose between epidermal and neural fates. Notch, a phylogenetically conserved transmembrane protein, may act as a receptor in a lateral signalling pathway in which a single neural precursor is chosen from each group and the neural fate of the other cells is inhibited, causing them to differentiate into epidermis. Possible intracellular transduction events mediating signals from Notch are, however, unknown. shaggy is also required for the lateral signal and encodes serine/threonine protein kinases with homology to the glycogen synthase kinase-3 (GSK-3) enzymes that act in signal transduction pathways in vertebrates. We report here that, in transgenic flies, GSK-3 beta can substitute for shaggy, and we also present a study of epistatic relationships between shaggy and gain and loss of function alleles of Notch. The results indicate that shaggy/GSK-3 is part of a signalling pathway downstream of Notch.
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PMID:Drosophila shaggy kinase and rat glycogen synthase kinase-3 have conserved activities and act downstream of Notch. 838 71

Several peptides derived from microtubule-associated tau protein, have been tested as substrates for glycogen synthase kinase 3 (GSK 3). In the absence of cofactors, GSK 3 can modify serines or threonines followed by prolines. In other cases, a phosphorylation in position +4 is required for the phosphorylation of threonine/serine residues. A third type of substrate can be modified by GSK 3 in the presence of heparin. The comparison of GSK 3 with other kinases suggests some similar features of this kinase with proline-directed protein kinases, such as cdc-2 or mitogen-activated protein kinase (MAP Kinases,) and also with casein kinase 2 (CK 2). Thus, all these kinases are specifically inhibited by 5,6-Dichloro-1-(beta-D-ribofuranosyl)-benzimidazole (DRB). However, heparin is an inhibitor of CK 2 whereas it activates the modification of certain substrates by GSK 3. A possible explanation for the obtained results is that the consensus sequence for GSK 3 phosphorylation is a serine/threonine adjacent to a proline or other beta-turn former residue and that such recognition could be favoured by the presence of adjacent negative charges or the addition of polyanions.
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PMID:Glycogen synthase kinase 3 phosphorylation of different residues in the presence of different factors: analysis on tau protein. 897 80

Sperm motility is regulated by protein phosphorylation. We have recently shown that a serine/threonine phosphatase system is involved in motility regulation. Two of the components of the phosphatase system, GSK-3 and PP1gamma2, are regulated by tyrosine phosphorylation. During our investigation of sperm tyrosine-phosphorylated proteins we discovered a 55-kDa protein whose tyrosine phosphorylation correlates closely to the motility state of sperm. This protein is tyrosine phosphorylated to a much higher degree in motile caudal than in immotile caput epididymal sperm. Motility inhibition of caudal epididymal sperm by protein kinase A (PKA) anchoring inhibition or by ionomycin-induced calcium overload led to the virtual disappearance of tyrosine phosphorylation of the 55-kDa protein. Conversely, treatment of sperm with motility activators, isobutylmethylxanthine or 8-bromo-cAMP, resulted in increased tyrosine phosphorylation of the protein. The protein was present in the soluble 100 000 x g supernatants of sperm extracts and was heat labile. Chromatography through diethylaminoethyl-cellulose and Western blot analysis showed that this 55-kDa protein is not a regulatory subunit of PKA or alpha-tubulin. Our results represent the identification of a soluble protein whose tyrosine phosphorylation varies directly with motility and suggest that motility regulation may involve cross talk between PKA, calcium, and tyrosine kinase pathways.
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PMID:A tyrosine-phosphorylated 55-kilodalton motility-associated bovine sperm protein is regulated by cyclic adenosine 3',5'-monophosphates and calcium. 916 97

The phosphorylation of insulin receptor substrate 1 (IRS-1) on tyrosine residues by the insulin receptor (IR) tyrosine kinase is involved in most of the biological responses of insulin. IRS-1 mediates insulin signaling by recruiting SH2 proteins through its multiple tyrosine phosphorylation sites. The phosphorylation of IRS-1 on serine/threonine residues also occurs in cells; however, the particular protein kinase(s) promoting this type of phosphorylation are unknown. Here we report that glycogen synthase kinase 3 (GSK-3) is capable of phosphorylating IRS-1 and that this modification converts IRS-1 into an inhibitor of IR tyrosine kinase activity in vitro. Expression of wild-type GSK-3 or an "unregulated" mutant of the kinase (S9A) in CHO cells overexpressing IRS-1 and IR, resulted in increased serine phosphorylation levels of IRS-1, suggesting that IRS-1 is a cellular target of GSK-3. Furthermore, insulin-induced tyrosine phosphorylation of IRS-1 and IR was markedly suppressed in cells expressing wild-type or the S9A mutant, indicating that expression of GSK-3 impairs IR tyrosine kinase activity. Taken together, our studies suggest a new role for GSK-3 in attenuating insulin signaling via its phosphorylation of IRS-1 and may provide new insight into mechanisms important in insulin resistance.
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PMID:Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin action. 927 79

When serum-starved A431 cells were treated with 200 nM phorbol ester TPA for 15 min, the cellular activity of protein kinase FA/glycogen synthase kinase-3alpha (kinase FA/GSK-3alpha) could be decreased to approximately 25% of control. Conversely, when treated with 1 microM TPA for 24 hr, the activity could be reversibly increased to approximately 200% of Control. The naturally occurring protein kinase C (PKC) inhibitor sphingosine at a concentration of 27 microM could also induce activation of kinase FA/GSK-3alpha to approximately 200% of control within 60 min. Further, when cells were chronically treated with 1 microM TPA for 24 hr and then with 27 microM sphingosine for 60 min, the activity of kinase FA/GSK-3alpha could only be increased to approximately 200% of control. Furthermore, when cells were pretreated with sphingosine and then acutely treated with TPA, the acute TPA effect on kinase FA/GSK-3alpha activity could be abolished by genistein or tyrosine phosphorylation, which could be blocked by genistein or tyrosine phosphatase, but could be reversed by orthovanadate. Taken together, the results demonstrate that TPA/sphingosine induce tyrosine phosphorylation and concurrent activation of kinase FA/GSK-3alpha in a common signalling pathway. Since TPA and sphingosine are potent PKC modulators, the results further suggest a potential role of PKC in modulating tyrosine phosphorylation/activation of kinase FA/GSK-3alpha. Kinetic studies on seven subtypes of PKC further demonstrate a specific involvement of PKCE in this tyrosine phosphorylation/activation process. This provides a new mode of signal transduction between these two important serine/threonine kinases in cells.
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PMID:The naturally occurring PKC inhibitor sphingosine and tumor promoter phorbol ester potentially induce tyrosine phosphorylation/activation of oncogenic proline-directed protein kinase FA/GSK-3alpha in a common signalling pathway. 949 24


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