Cdc2 Kinase Directly Phosphorylates the cis-Golgi Matrix Protein GM130 and Is Required for Golgi Fragmentation in Mitosis

Lowe, Martin; Rabouille, Cathérine; Nakamura, Nobuhiro; Watson, Rose; Jackman, Mark; Jämsä, Eija; Rahman, Dinah; Pappin, Darryl; Warren, Graham

doi:10.1016/s0092-8674(00)81737-7

Cited by 279 publications

(316 citation statements)

References 35 publications

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“…[91][92][93] The very C-terminus of GM130 may bind to and stimulate the catalytic activity of HtrA1, a serine protease that inhibits TGF-b signaling. 94 EspG proteins produced by enteric pathogens may interact with GM130 and disrupt protein secretion of the host cells.…”

Section: Gcks In Immune Regulationmentioning

confidence: 99%

Germinal center kinases in immune regulation

Yin

Shi

et al. 2012

Cell Mol Immunol

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Section: Gcks In Immune Regulationmentioning

confidence: 99%

Germinal center kinases in immune regulation

Yin

Shi

et al. 2012

Cell Mol Immunol

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“…In that regard, the mammalian Golgi complex is disassembled from its pericentriolar disposition by a highly regulated course of mitotic fragmentation involving mitogen-activated protein (MAP) kinase and polo-like kinase pathways (Nelson, 2000;Rossanese and Glick, 2001;Colanzi et al, 2003a,b;Ruan et al, 2004;Xie et al, 2004), and they are subsequently further vesiculated in a Cdc2-dependent manner (Lowe et al, 1998). The dispersed Golgi membranes in hSac1-depleted cells bear a superficial resemblance to those adopted by Golgi membranes during a normal course of mitosis.…”

Section: Sac1 and Progression Through The Cell Cyclementioning

confidence: 99%

The Sac1 Phosphoinositide Phosphatase Regulates Golgi Membrane Morphology and Mitotic Spindle Organization in Mammals

Liu

Boukhelifa

Tribble

et al. 2008

MBoC

131

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Phosphoinositides (PIPs) are ubiquitous regulators of signal transduction events in eukaryotic cells. PIPs are degraded by various enzymes, including PIP phosphatases. The integral membrane Sac1 phosphatases represent a major class of such enzymes. The central role of lipid phosphatases in regulating PIP homeostasis notwithstanding, the biological functions of Sac1-phosphatases remain poorly characterized. Herein, we demonstrate that functional ablation of the single murine Sac1 results in preimplantation lethality in the mouse and that Sac1 insufficiencies result in disorganization of mammalian Golgi membranes and mitotic defects characterized by multiple mechanically active spindles. Complementation experiments demonstrate mutant mammalian Sac1 proteins individually defective in either phosphoinositide phosphatase activity, or in recycling of the enzyme from the Golgi system back to the endoplasmic reticulum, are nonfunctional proteins in vivo. The data indicate Sac1 executes an essential household function in mammals that involves organization of both Golgi membranes and mitotic spindles and that both enzymatic activity and endoplasmic reticulum localization are important Sac1 functional properties. INTRODUCTIONSpatial and temporal regulation of intracellular signaling in eukaryotic cells involves the compartmentalization of membrane surfaces into discrete, albeit often transient, functional units. There are several biochemical strategies by which cells generate such units or domains. One well-established strategy uses the chemical diversity offered by phosphoinositides (PIPs), i.e., phosphorylated forms of phosphatidylinositol (PtdIns) (Majerus, 1997;Fruman et al., 1998;Strahl and Thorner, 2007). The chemical heterogeneity of individual PIP species permits the construction of chemically unique platforms on membrane surfaces that, in turn, recruit unique cohorts of proteins that drive specific biological reactions. Spatial and temporal control of such reactions requires a finely coordinated balance between the activities of the lipid kinases that produce PIPs and the activities of enzymes that degrade them. PIP turnover is catalyzed by two general classes of enzymes: phospholipases and PIP phosphatases.Although experimental scrutiny of the phospholipases has historically been more intense, recent demonstrations of the significant biological functions played by PTEN, the myotubularins, and synaptojanins highlight the general importance of PIP phosphatases (Wishart et al., 2001;Wishart and Dixon, 2002;Wenk and De Camilli, 2004).The SAC domain derives from the yeast Sac1 protein (ySac1; Cleves et al., 1989), and it represents a signature for PIP phosphatase catalytic activity . PIP phosphatases such as phosphatase and tensin homolog (mutated in multiple advanced cancers 1) (PTEN) (Maehama et al., 2001), synaptojanins (Cremona et al., 1999), and synaptojanin-like proteins (Srinivasan et al., 1997;Stolz et al., 1998) all harbor SAC domains. The prototypical member of this family, ySac1, catalyzes the dephosphoryla...

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“…Alternatively, the Vps52/53/54 complex could be required to maintain the integrity of the TGN. The two possibilities are not mutually exclusive: GM130 functions both as a docking factor, interacting with p115 in intra-Golgi transport in mammalian cells, and as a matrix protein, mediating the assembly and disassembly of stacked Golgi cisternae through successive cell divisions coupled to a cycle of phosphorylation/dephosphorylation (Nakamura et al, 1997;Lowe et al, 1998). The isolation of temperature-sensitive-forfunction alleles of vps52, vps53, and vps54 should help in separating the direct effects of these mutations from those resulting from long-term loss of late Golgi function.…”

Section: Function Of the Vps52/53/54 Complex In Golgi Sortingmentioning

confidence: 99%

Vps52p, Vps53p, and Vps54p Form a Novel Multisubunit Complex Required for Protein Sorting at the Yeast Late Golgi

Conibear

Stevens

2000

MBoC

267

336

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The late Golgi of the yeast Saccharomyces cerevisiae receives membrane traffic from the secretory pathway as well as retrograde traffic from post-Golgi compartments, but the machinery that regulates these vesicle-docking and fusion events has not been characterized. We have identified three components of a novel protein complex that is required for protein sorting at the yeast late Golgi compartment. Mutation of VPS52, VPS53, or VPS54 results in the missorting of 70% of the vacuolar hydrolase carboxypeptidase Y as well as the mislocalization of late Golgi membrane proteins to the vacuole, whereas protein traffic through the early part of the Golgi complex is unaffected. A vps52/53/54 triple mutant strain is phenotypically indistinguishable from each of the single mutants, consistent with the model that all three are required for a common step in membrane transport. Native coimmunoprecipitation experiments indicate that Vps52p, Vps53p, and Vps54p are associated in a 1:1:1 complex that sediments as a single peak on sucrose velocity gradients. This complex, which exists both in a soluble pool and as a peripheral component of a membrane fraction, colocalizes with markers of the yeast late Golgi by immunofluorescence microscopy. Together, the phenotypic and biochemical data suggest that VPS52, VPS53, and VPS54 are required for the retrograde transport of Golgi membrane proteins from an endosomal/ prevacuolar compartment. The Vps52/53/54 complex joins a growing list of distinct multisubunit complexes that regulate membrane-trafficking events.

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Cdc2 Kinase Directly Phosphorylates the cis-Golgi Matrix Protein GM130 and Is Required for Golgi Fragmentation in Mitosis

Cited by 279 publications

References 35 publications

Germinal center kinases in immune regulation

Germinal center kinases in immune regulation

The Sac1 Phosphoinositide Phosphatase Regulates Golgi Membrane Morphology and Mitotic Spindle Organization in Mammals

Vps52p, Vps53p, and Vps54p Form a Novel Multisubunit Complex Required for Protein Sorting at the Yeast Late Golgi

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