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Mol Cell Biol
2011 Jun 01;3111:2262-75. doi: 10.1128/MCB.00753-10.
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Characterization of the mechanisms controlling Greatwall activity.
Vigneron S
,
Gharbi-Ayachi A
,
Raymond AA
,
Burgess A
,
Labbé JC
,
Labesse G
,
Monsarrat B
,
Lorca T
,
Castro A
.
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Here we investigate the mechanisms regulating Greatwall (Gwl), a serine/threonine kinase essential for promoting the correct timing of mitosis. We identify Gwl as a unique AGC kinase that, unlike most AGC members, appears to be devoid of a hydrophobic motif despite the presence of a functional hydrophobic pocket. Our results suggest that Gwl activation could be mediated by the binding of its hydrophobic pocket to the hydrophobic motif of another AGC kinase. Our molecular modeling and mutagenic analysis also indicate that Gwl displays a conserved tail/linker site whose phosphorylation mediates kinase activation by promoting the interaction of this phosphorylated residue with two lysines at the N terminus. This interaction could stabilize the αC-helix and maintain kinase activity. Finally, the different phosphorylation sites on Gwl are identified, and the role of each one in the regulation of Gwl kinase activity is determined. Our data suggest that only the phosphorylation of the tail/linker site, located outside the putative T loop, appears to be essential for Gwl activation. In summary, our results identify Gwl as a member of the AGC family of kinases that appears to be regulated by unique mechanisms and that differs from the other members of this family.
Aimes,
Serine-53 at the tip of the glycine-rich loop of cAMP-dependent protein kinase: role in catalysis, P-site specificity, and interaction with inhibitors.
2000, Pubmed
Aimes,
Serine-53 at the tip of the glycine-rich loop of cAMP-dependent protein kinase: role in catalysis, P-site specificity, and interaction with inhibitors.
2000,
Pubmed
Archambault,
Mutations in Drosophila Greatwall/Scant reveal its roles in mitosis and meiosis and interdependence with Polo kinase.
2007,
Pubmed
,
Xenbase
Biondi,
The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB.
2001,
Pubmed
Biondi,
Identification of a pocket in the PDK1 kinase domain that interacts with PIF and the C-terminal residues of PKA.
2000,
Pubmed
Brendel,
Methods and algorithms for statistical analysis of protein sequences.
1992,
Pubmed
Burgess,
Loss of human Greatwall results in G2 arrest and multiple mitotic defects due to deregulation of the cyclin B-Cdc2/PP2A balance.
2010,
Pubmed
Casamayor,
Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo.
1999,
Pubmed
Castilho,
The M phase kinase Greatwall (Gwl) promotes inactivation of PP2A/B55delta, a phosphatase directed against CDK phosphosites.
2009,
Pubmed
,
Xenbase
Castro,
Cyclin B/cdc2 induces c-Mos stability by direct phosphorylation in Xenopus oocytes.
2001,
Pubmed
,
Xenbase
Cole,
The Jpred 3 secondary structure prediction server.
2008,
Pubmed
Dephoure,
A quantitative atlas of mitotic phosphorylation.
2008,
Pubmed
Frödin,
A phosphoserine/threonine-binding pocket in AGC kinases and PDK1 mediates activation by hydrophobic motif phosphorylation.
2002,
Pubmed
Gharbi-Ayachi,
The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting protein phosphatase 2A.
2010,
Pubmed
,
Xenbase
Glotzer,
Cyclin is degraded by the ubiquitin pathway.
1991,
Pubmed
,
Xenbase
Gould,
The chaperones Hsp90 and Cdc37 mediate the maturation and stabilization of protein kinase C through a conserved PXXP motif in the C-terminal tail.
2009,
Pubmed
Hauge,
RSK and MSK in MAP kinase signalling.
2006,
Pubmed
Hauge,
Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation.
2007,
Pubmed
Hirai,
Catalytic assessment of the glycine-rich loop of the v-Fps oncoprotein using site-directed mutagenesis.
2000,
Pubmed
Huse,
The conformational plasticity of protein kinases.
2002,
Pubmed
Kannan,
Did protein kinase regulatory mechanisms evolve through elaboration of a simple structural component?
2005,
Pubmed
Kannan,
The hallmark of AGC kinase functional divergence is its C-terminal tail, a cis-acting regulatory module.
2007,
Pubmed
Komander,
Role of T-loop phosphorylation in PDK1 activation, stability, and substrate binding.
2005,
Pubmed
Kozma,
Regulation of cell size in growth, development and human disease: PI3K, PKB and S6K.
2002,
Pubmed
Lorca,
Fizzy is required for activation of the APC/cyclosome in Xenopus egg extracts.
1998,
Pubmed
,
Xenbase
Lorca,
Constant regulation of both the MPF amplification loop and the Greatwall-PP2A pathway is required for metaphase II arrest and correct entry into the first embryonic cell cycle.
2010,
Pubmed
,
Xenbase
Manning,
The protein kinase complement of the human genome.
2002,
Pubmed
Mochida,
Regulated activity of PP2A-B55 delta is crucial for controlling entry into and exit from mitosis in Xenopus egg extracts.
2009,
Pubmed
,
Xenbase
Mora,
PDK1, the master regulator of AGC kinase signal transduction.
2004,
Pubmed
Olsen,
Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
2010,
Pubmed
Parekh,
Multiple pathways control protein kinase C phosphorylation.
2000,
Pubmed
Pearce,
The nuts and bolts of AGC protein kinases.
2010,
Pubmed
Peterson,
Kinase phosphorylation: Keeping it all in the family.
1999,
Pubmed
Söding,
Protein homology detection by HMM-HMM comparison.
2005,
Pubmed
Vigneron,
Kinetochore localization of spindle checkpoint proteins: who controls whom?
2004,
Pubmed
,
Xenbase
Vigneron,
Greatwall maintains mitosis through regulation of PP2A.
2009,
Pubmed
,
Xenbase
Vigneron,
Correction for Vigneron et al., "Characterization of the Mechanisms Controlling Greatwall Activity".
2017,
Pubmed
Wilm,
Femtomole sequencing of proteins from polyacrylamide gels by nano-electrospray mass spectrometry.
1996,
Pubmed
Yang,
Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation.
2002,
Pubmed
Yu,
Greatwall kinase: a nuclear protein required for proper chromosome condensation and mitotic progression in Drosophila.
2004,
Pubmed
Yu,
Greatwall kinase participates in the Cdc2 autoregulatory loop in Xenopus egg extracts.
2006,
Pubmed
,
Xenbase
Zhao,
Roles of Greatwall kinase in the regulation of cdc25 phosphatase.
2008,
Pubmed
,
Xenbase
