Phosphorylation of golgin-160 by mixed lineage kinase 3

Cha, Hyuk‐Jin; Smith, Barbara L.; Gallo, Kathleen A.; Machamer, Carolyn E.; Shapiro, Paul

doi:10.1242/jcs.00897

Cited by 27 publications

(19 citation statements)

References 36 publications

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“…A limitation of these experiments is that these cleavage products were not presented to the cell in the same way that they would be when naturally produced during apoptosis. Golgin-160 is phosphorylated in its N-terminal head domain (Cha et al, 2004) and transfected constructs may not be phosphorylated in the same manner as cleavage products made from Golgi-localized golgin-160. Also, the golgin-160 fragments were expressed in cells individually and not in combination, as they might be produced during apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory Pathway Stress and Ligation of Death Receptors

Maag

Mancini

Rosen

et al. 2005

MBoC

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Golgin-160 is a coiled-coil protein on the cytoplasmic face of the Golgi complex that is cleaved by caspases during apoptosis. We assessed the sensitivity of cell lines stably expressing wild-type or caspase-resistant golgin-160 to several proapoptotic stimuli. Cells expressing a caspase-resistant mutant of golgin-160 were strikingly resistant to apoptosis induced by ligation of death receptors and by drugs that induce endoplasmic reticulum (ER) stress, including brefeldin-A, dithiothreitol, and thapsigargin. However, both cell lines responded similarly to other proapoptotic stimuli, including staurosporine, anisomycin, and etoposide. The caspase-resistant golgin-160 dominantly prevented cleavage of endogenous golgin-160 after ligation of death receptors or induction of ER stress, which could be explained by a failure of initiator caspase activation. The block in apoptosis in cells expressing caspase-resistant golgin-160 could not be bypassed by expression of potential caspase cleavage fragments of golgin-160, or by drug-induced disassembly of the Golgi complex. Our results suggest that some apoptotic signals (including those initiated by death receptors and ER stress) are sensed and integrated at Golgi membranes and that golgin-160 plays an important role in transduction of these signals. INTRODUCTIONThe Golgi complex is central to the regulation of membrane trafficking in eukaryotic cells. It is the primary site for sorting and processing of proteins undergoing both exocytosis and endocytosis (reviewed in Farquhar and Palade, 1998). Under normal conditions, the mammalian Golgi complex is a collection of stacks of cisternal membranes near the microtubule organizing center. Proteins traversing the secretory pathway enter the Golgi at the cis face, are processed as they pass through the Golgi stacks, and are sorted at the trans face into vesicles bound for their intended destinations. The trans-Golgi is also important in sorting proteins being endocytosed or cycling between the plasma membrane and intracellular membrane compartments. This affords the Golgi extensive communication with the rest of the cell and its surroundings, placing it in a prime position to sense and integrate information about the state of the cell and its environment.The structure of the Golgi is highly dynamic, allowing reversible disassembly during mitosis. Key secretory pathway proteins are phosphorylated in a cell cycle-dependent manner to stop membrane trafficking and disassemble the Golgi (reviewed in Rabouille and Jokitalo, 2003). This rearrangement from a single perinuclear organelle to dispersed vesiculated compartments is thought to ensure partitioning of the Golgi complex into both daughter cells during cytokinesis. When Golgi disassembly is prevented by addition of antibodies to Golgi reassembly and stacking protein of 65 kDa (GRASP65), cells complete S phase, but they are unable to enter mitosis. This mitotic block can be bypassed by disassembling the Golgi with drugs (Sutterlin et al., 2002). Once mitosis is complete, the Golgi...

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Section: Discussionmentioning

confidence: 99%

Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory Pathway Stress and Ligation of Death Receptors

Maag

Mancini

Rosen

et al. 2005

MBoC

Self Cite

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“…Given recent data regarding Ras signaling on endosomes as well as on the plasma membrane (48 -51) and considering the ability of both Cdc42 (47,52) and MLK3 to localize to endomembrane structures (40), it would not be at all surprising if under certain conditions Cdc42 activates MLK3 on these cellular membranes.…”

Section: Discussionmentioning

confidence: 99%

Cdc42 Induces Activation Loop Phosphorylation and Membrane Targeting of Mixed Lineage Kinase 3

Du¹,

Böck²,

Schachter³

et al. 2005

Journal of Biological Chemistry

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Mixed lineage kinase 3 (MLK3) functions as a mitogen-activated protein kinase kinase kinase to activate multiple mitogen-activated protein kinase pathways. Our current studies demonstrate that lack of MLK3 blocks signaling of activated Cdc42 to c-Jun N-terminal kinase, giving strong support for the idea that Cdc42 is a physiological activator of MLK3. We show herein that Cdc42, in a prenylationdependent manner, targets MLK3 from a perinuclear region to membranes, including the plasma membrane. Cdc42-induced membrane targeting of MLK3 is independent of MLK3 catalytic activity but depends upon an intact Cdc42/Rac-interactive binding motif, consistent with MLK3 membrane translocation being mediated through direct binding of Cdc42. Phosphorylation of the activation loop of MLK3 requires MLK3 catalytic activity and is induced by Cdc42 in a prenylation-independent manner, arguing that Cdc42 binding is sufficient for activation loop autophosphorylation of MLK3. However, membrane targeting is necessary for full activation of MLK3 and maximal signaling to JNK. We previously reported that MLK3 is autoinhibited through an interaction between its N-terminal SH3 domain and a proline-containing sequence found between the leucine zipper and the CRIB motif of MLK3. Thus we propose a model in which GTP-bound Cdc42/Rac binds MLK3 and disrupts SH3-mediated autoinhibition leading to dimerization and activation loop autophosphorylation. Targeting of this partially active MLK3 to membranes likely results in additional phosphorylation events that fully activate MLK3 and its ability to maximally signal through the JNK pathway.

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“…Furthermore, we have recently shown that the CRISP domain of mouse CRISP2 interacts with MAP kinase kinase kinase 11 (MAP3K11; . MAP3K11 is a kinase with a role in activating the Jun NH 2 -terminal kinase signaling (Chang & Karin 2001, Huang & Zhang 2003, Huynh et al 2003 or in phosphorylating non-signal transduction proteins as exemplified by Golgi-associated protein, golgin-60, in somatic cells (Cha et al 2004). CRISP2 and MAP3K11 are co-localized within the mouse sperm acrosome .…”

Section: Introductionmentioning

confidence: 99%

Characterization of gametogenetin 1 (GGN1) and its potential role in male fertility through the interaction with the ion channel regulator, cysteine-rich secretory protein 2 (CRISP2) in the sperm tail

Jamsai

Bianco²,

Smith³

et al. 2008

Reproduction

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Cysteine-rich secretory protein 2 (CRISP2) is a testis-enriched protein localized to the sperm acrosome and tail. CRISP2 has been proposed to play a critical role in spermatogenesis and male fertility, although the precise function(s) of CRISP2 remains to be determined. Recent data have shown that the CRISP domain of the mouse CRISP2 has the ability to regulate Ca 2C flow through ryanodine receptors (RyR) and to bind to MAP kinase kinase kinase 11 (MAP3K11). To further define the biochemical pathways within which CRISP2 is involved, we screened an adult mouse testis cDNA library using a yeast two-hybrid assay to identify CRISP2 interacting partners. One of the most frequently identified CRISP2-binding proteins was gametogenetin 1 (GGN1). Interactions occur between the ion channel regulatory region within the CRISP2 CRISP domain and the carboxyl-most 158 amino acids of GGN1. CRISP2 does not bind to the GGN2 or GGN3 isoforms. Furthermore, we showed that Ggn1 is a testis-enriched mRNA and the protein first appeared in late pachytene spermatocytes and was up-regulated in round spermatids before being incorporated into the principal piece of the sperm tail where it co-localized with CRISP2. These data along with data on RyR and MAP3K11 binding define the CRISP2 CRISP domain as a protein interaction motif and suggest a role for the GGN1-CRISP2 complex in sperm tail development and/or motility.Reproduction (2008) 135 751-759

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Phosphorylation of golgin-160 by mixed lineage kinase 3

Cited by 27 publications

References 36 publications

Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory Pathway Stress and Ligation of Death Receptors

Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory Pathway Stress and Ligation of Death Receptors

Cdc42 Induces Activation Loop Phosphorylation and Membrane Targeting of Mixed Lineage Kinase 3

Characterization of gametogenetin 1 (GGN1) and its potential role in male fertility through the interaction with the ion channel regulator, cysteine-rich secretory protein 2 (CRISP2) in the sperm tail

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