| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.87653174 |
| As expected , overexpressed Munc18c was found to co immunoprecipitate with syntaxin 4 in the basal state . 0.87653174^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| However , the syntaxin 4 binding protein , Munc18c , was targeted by O linked glycosylation . ^^^ |
|
| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| The disruption of Munc18c binding to syntaxin 4 impairs insulin stimulated GLUT 4 vesicle translocation in 3T3L1 adipocytes . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.67391342 |
| In these cells , Munc18c was predominantly associated with syntaxin 4 , although it bound both syntaxin 2 and syntaxin 4 to similar extents in vitro . 0.67391342^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :1.0708651 |
| These data thus identify a region of munc18c between residues 1 and 139 as a minimal domain for its interaction with syntaxin 4 . . 1.0708651^^^ To investigate the domains of munc18c responsible for its interaction with syntaxin 4 , fragments of munc18c were generated and their interaction with syntaxin 4 examined in vivo by the yeast two hybrid assay . 0.98001918^^^ Definition of a minimal munc18c domain that interacts with syntaxin 4 . munc18c is a critical protein involved in trafficking events associated with syntaxin 4 and which also mediates inhibitory effects on vesicle docking and / or fusion . 0.70876895^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.68475683 |
| The protein protein interaction between syntaxin 4 and VAMP 2 with their transmembrane domains was markedly inhibited on coexpression of munc18c . 0.68475683^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.77725495 |
| The SM protein Munc18c was shown to interact with the Syntaxin 4 monomer , Syntaxin 4 containing SNARE complexes , and the Syntaxin4 / Tomosyn complex . 0.77725495^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| This platelet Sec 1 protein ( PSP ) bound to syntaxin 4 and thereby excluded the binding of SNAP 25 with syntaxin 4 , an interaction critical to vesicle docking . ^^^ Phosphorylation by PKC in vitro inhibited PSP from binding to syntaxin 4 . ^^^ The PKC dependent phosphorylation of PSP in activated platelets and its inhibitory effects on syntaxin 4 binding provide a novel functional link that may be important in coupling the processes of cell activation , intracellular signaling , and secretion . . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| We found that mast cells express Munc 18 2 , which interacts with target SNAREs syntaxin 2 or 3 , as well as Munc 18 3 , which interacts with syntaxin 4 . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Syntaxin 4 binding Munc 18 3 was absent , whereas small amounts of the syntaxin 3 interacting partner Munc 18 2 consistently distributed into rafts . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Furthermore , an association between Munc18c ( Munc 18 3 ) and syntaxin 4 has been reported . ^^^ Munc 18 3 was localized on the apical plasma membrane where exocytosis occurs and interacted with syntaxin 4 . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Characterization of Munc 18c and syntaxin 4 in 3T3 L 1 adipocytes . ^^^ The specific interaction between Munc 18c and syntaxin 4 is of interest because aside from syntaxin 1A , which is not expressed in adipocytes , syntaxin 4 is the only syntaxin that binds to VAMP 2 . ^^^ Using a three way binding assay , it was shown that Munc 18c inhibits the binding of syntaxin 4 to VAMP 2 . ^^^ The subcellular distribution of syntaxin 4 and Munc 18c was almost identical , both being enriched in the plasma membrane , and both exhibiting an insulin dependent movement out of an intracellular membrane fraction similar to that observed for GLUT 4 . ^^^ These data suggest that syntaxin 4 / Munc 18c / VAMP 2 may play a role in the docking / fusion of intracellular GLUT 4 containing vesicles with the cell surface in adipocytes . . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Inhibition of the binding of SNAP 23 to syntaxin 4 by Munc18c . ^^^ Expression of SNAP 23 , syntaxin 4 , and the syntaxin binding protein Munc 18c in COS cells revealed that Munc18c reduced the amount of SNAP 23 bound to syntaxin 4 in a concentration dependent manner . ^^^ These results suggest that the binding of SNAP 23 to syntaxin 4 is inhibited by Munc18c in adipocytes . . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Platelet levels of SCAMPS ( secretory carrier membrane proteins ) , Rab 11 , Rab 31 , NSF ( N ethylmaleimide sensitive fusion protein ) , syntaxin 2 , syntaxin 4 , munc18c , and p115 / TAP ( p115 / transcytosis associated protein ) were not significantly altered in several different HPS mutants . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| To examine the functional role of the interaction between Munc18c and syntaxin 4 in the regulation of GLUT 4 translocation in 3T3L1 adipocytes , we assessed the effects of introducing three different peptide fragments ( 20 to 24 amino acids ) of Munc18c from evolutionarily conserved regions of the Sec 1 protein family predicted to be solvent exposed . ^^^ One peptide , termed 18c / pep3 , inhibited the binding of full length Munc18c to syntaxin 4 , whereas expression of the other two peptides had no effect . ^^^ Together , these data suggest that the interaction between Munc18c and syntaxin 4 is required for the integration of GLUT 4 and IRAP storage vesicles into the plasma membrane but is not necessary for the insulin stimulated trafficking to and association with the cell surface . . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Inversely , when syntaxin 4 was immunoprecipitated from parotid lysates , SNAP 23 , Munc18c , and N ethylmaleimide sensitive fusion protein ( NSF ) were coprecipitated , but VAMP 2 was again undetectable . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Studies have identified key roles for vesicle associated membrane protein 2 ( VAMP 2 ) and syntaxin 4 in this event , and more recently have also implicated SNAP 23 and Munc18c in this process . ^^^ Such analyses suggest that in 3T3 L 1 adipocytes there are approximately 374 , 000 copies of syntaxin 4 , 1 . 15 10 10 ( 6 ) copies of SNAP 23 , 495 , 000 copies of VAMP 2 , 4 . 3 10 10 ( 6 ) copies of cellubrevin and 452 , 000 copies of Munc18c per cell , compared to previous estimates of 280 , 000 copies of Glut 4 . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Moreover , Munc18c / WT bound to syntaxin 4 at both 23 and 37 degrees C whereas Munc18c / TS bound syntaxin 4 only at 23 degrees C . ^^^ This was due to a temperature dependent conformational change in Munc18c / TS , as its ability to bind syntaxin 4 and effects on GLUT 4 translocation were rapidly reversible while protein expression levels remained unchanged . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Consistent with previous studies in adipocytes , overexpression of the syntaxin 4 binding Munc18c isoform , but not the related Munc18b isoform , in vivo specifically inhibited insulin stimulated GLUT 4 EGFP translocation . ^^^ The ability of Munc18c to block GLUT 4 EGFP translocation to the transverse tubule membrane but not the sarcolemma membrane was consistent with substantially reduced levels of syntaxin 4 in the transverse tubule membrane . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Munc18c has been shown to bind syntaxin 4 and to play a role in GLUT 4 translocation and glucose transport , although this role is as yet poorly defined . ^^^ Mutagenesis of a potential proline directed kinase phosphorylation site in munc18c , T 569 , that in previous studies of its neuronal counterpart munc18a caused its dissociation from its complex with syntaxin 1a , had no effect on munc18c ' s association with syntaxin 4 or its inhibition of glucose transport , indicative that phosphorylation of this residue is not important for insulin regulation of glucose transport . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| A subset of t SNAREs ( Syntaxin 4 / SNAP23 / Munc18c ) known to control regulated exocytosis in other cell types was substantially increased by LPS in a temporal pattern coinciding with peak TNFalpha secretion . ^^^ Syntaxin 4 formed a complex with Munc18c at the cell surface of macrophages . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Platelet membranes contain Munc18c syntaxin 4 complexes , but minimal if any Munc18c syntaxin 2 complexes were found . ^^^ Munc18c syntaxin 4 complexes were dissociated when cells were activated to secrete . ^^^ Two potential inhibitors of Munc18c syntaxin 4 complexes were generated to examine whether complex dissociation may lead to exocytosis . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| To investigate the physiological effects of modulating the abundance of Munc18c or syntaxin 4 ( Syn 4 ) proteins on the regulation of glucose homeostasis in vivo , we generated tetracycline repressible transgenic mice that overexpress either Munc18c or Syn 4 proteins in skeletal muscle , pancreas and adipose tissue seven , five , and threefold over endogenous protein , respectively . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Recombinant expression of Munc18c in a baculovirus system and interaction with syntaxin 4 . ^^^ Recombinant Munc18c produced in this way is functional , in that it forms a stable complex with the SNARE interacting partner , syntaxin 4 . ^^^ We have also developed a method to purify the Munc18c : syntaxin 4 complex . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| We had reported that in the rat pancreas , Munc18c co localizes with t SNAREs syntaxin 4 and SNAP 23 on the acinar cell basolateral plasma membrane . ^^^ |
|
| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Insulin stimulated translocation of GLUT 4 vesicles from an intracellular compartment to the plasma membrane in 3T3L1 adipocytes is mediated through a syntaxin 4 ( Syn 4 ) and Munc18c dependent mechanism . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Protease activated receptor 1 activation of endothelial cells induces protein kinase Calpha dependent phosphorylation of syntaxin 4 and Munc18c : role in signaling p selectin expression . ^^^ We identified the presence of syntaxin 4 , syntaxin 3 , and the high affinity syntaxin 4 regulatory protein Munc18c in human lung microvascular endothelial cells . ^^^ Thrombin ligation of protease activated receptor 1 activated the phosphorylation of syntaxin 4 and Munc18c , which , in turn , disrupted the interaction between syntaxin 4 and Munc 18 . ^^^ Protein kinase Calpha activation was required for the phosphorylation of syntaxin 4 and Munc18c as well as the cell surface expression of P selectin . ^^^ Thus , protease activated receptor 1 induced protein kinase Calpha activation and phosphorylation of syntaxin 4 and Munc18c are required for the cell surface expression of P selectin and the consequent binding of neutrophils to endothelial cells . . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| We have now generated mouse embryos deficient in the syntaxin 4 binding protein Munc18c and show that the insulin induced appearance of GLUT 4 at the cell surface is enhanced in adipocytes derived from these Munc18c / mice compared with that in Munc18c+ / + cells . ^^^ These findings demonstrate that Munc18c inhibits insulin stimulated externalization of GLUT 4 in a wortmannin sensitive manner , and they suggest that disruption of the interaction between syntaxin 4 and Munc18c in adipocytes might result in enhancement of insulin stimulated GLUT 4 externalization . . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| At the cell periphery , GLUT 4 containing vesicles tether , dock , and fuse with the PM assisted by the exocyst complex followed by engagement of a soluble N ethylmaleimide sensitive factor attachment protein receptor ( SNARE ) complex [ with vesicle associated membrane protein ( VAMP ) 2 as the vesicular ( 5 ) SNARE and soluble NSF attachment protein ( SNAP ) 23 and syntaxin 4 as target ( t ) SNAREs ] regulated by the accessory proteins Munc18c , Synip and Tomosyn . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Upon macrophage activation , syntaxin 4 was recruited to cholesterol dependent lipid rafts , whereas its regulatory protein , Munc18c , was excluded from the rafts . ^^^ |
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| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| Stimulus induced tyrosine phosphorylation of Munc18c was investigated as a potential regulatory mechanism by which the Munc18c Syntaxin 4 complex can be dissociated in response to divergent stimuli in multiple cell types . ^^^ Syntaxin 4 binding to Munc18c decreased as Munc18c phosphorylation levels increased in pervanadate treated cells , suggesting that phosphorylation dissociates the Munc18c Syntaxin 4 complex . ^^^ Mutagenesis of one residue in this region , Y219F , significantly increased the affinity of Munc18c for Syntaxin 4 , whereas mutation of three other candidate sites was without effect . ^^^ These data support a novel and conserved mechanism for the dissociation of Munc18c Syntaxin 4 complexes in a stimulus dependent manner to facilitate the increase in Syntaxin 4 VAMP 2 association and to promote vesicle / granule fusion . . ^^^ |
|
| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O00186 and Q12846 |
Pubmed |
SVM Score :0.0 |
| NA |
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