Mastoparan stimulates exocytosis at a Ca(2+)-independent late site in stimulus-secretion coupling. Studies with the RINm5F beta-cell line.

Komatsu, Mitsuhisa; McDermott, Alison M.; Gillison, S. L.; Sharp, Geoffrey W. G.

doi:10.1016/s0021-9258(19)49462-3

Cited by 69 publications

(10 citation statements)

References 49 publications

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“…It has been reported recently that mastoparan, a tetradecapeptide from wasp venom (Hagashijima et al, 1990), stimulates the catalytic as well as phosphoenzyme formation of NDP kinase in rat liver cytosol (Kikkawa et al, 1992). Therefore, it is of interest that studies from several laboratories (Jones et al, 1993;Komatsu et al, 1993), including our own (current studies; Metz et al, 1993b) have demonstrated that mastoparan stimulates insulin secretion from isolated rat islets as well as from pure cell lines by an unidentified mechanism. Furthermore, we observed that this peptide, in insulinotropic concentrations (30 /uM), stimulated NDP kinase activity in islets.…”

Section: Discussionmentioning

confidence: 79%

Characterization of Nucleoside Diphosphokinase Activity in Human and Rodent Pancreatic .beta. Cells: Evidence for Its Role in the Formation of Guanosine Triphosphate, a Permissive Factor for Nutrient-Induced Insulin Secretion

Kowluru¹,

Metz²

1994

Biochemistry

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We have recently demonstrated a permissive role for GTP in nutrient-induced insulin secretion. One of the possible loci at which GTP might exert its regulatory effects include one (or more) of the GTP-binding proteins which we have identified in subcellular fractions (including secretory granules) of pancreatic islets. Herein, we characterize nucleoside diphosphokinase (NDP kinase) activity, which catalyzes the transphosphorylation of nucleotide diphosphate (e.g., GDP) to nucleotide triphosphates (e.g., GTP) in insulin-secreting cells. The presence of NDP kinase activity in normal rat and human islets, and pure beta (RIN and HIT) cells, was verified by three distinct approaches: first, its catalytic activity (formation of GTP or GTP gamma S from GDP and ATP or ATP gamma S); secondly, by immunologic detection; and third, by quantitating the phosphoenzyme intermediate of NDP kinase, which is involved in a ping-pong phosphotransfer mechanism. Subcellularly, NDP kinase is predominantly cytosolic (with a tetrameric molecular mass of 85-90 kDa) and requires divalent metal ions and thiols for its activity. UDP, which forms an abortive complex with the enzyme, inhibited its activity in a concentration-dependent manner (Ki = 2 mM). The phosphorylated intermediate of NDP kinase was differentially sensitive to heat, acidic pH, and a histidine-selective reagent, diethyl pyrocarbonate, suggesting that (one of) the phosphoamino acid(s) may be histidine. These data demonstrate that in beta cells NDP kinase undergoes transient phosphorylation and suggest that this phosphate, in turn, is transferred to GDP. If the GTP which is formed thereby is bound to, or channelled to, relevant GTP-binding proteins, it would facilitate the formation of active form of these proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 79%

Characterization of Nucleoside Diphosphokinase Activity in Human and Rodent Pancreatic .beta. Cells: Evidence for Its Role in the Formation of Guanosine Triphosphate, a Permissive Factor for Nutrient-Induced Insulin Secretion

Kowluru¹,

Metz²

1994

Biochemistry

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“…Additionally, there is a single report that mastoparan can activate the low molecular weight Rho protein (). One of the primary consequences of mastoparan action in pancreatic β-cells is the stimulation of exocytosis ( − ). Unlike other stimulants of insulin release from the β-cell, mastoparan has a unique mode of action in that neither the activation of protein kinases A and C nor the involvement of phospholipase A 2 is required ().…”

Section: Discussionmentioning

confidence: 99%

“…Our data indicate that mastoparan stimulates the exchange of labeled GDP for cold GTP and appears to corroborate previous data by Koch et al () with purified Rho protein. While mastoparan-stimulated insulin release in Wistar rat islets ( , ), as well as in clonal beta cells such as βTC-3 (), seems to involve a pertussis toxin- (PTX-) sensitive mechanism, the effect of PTX on insulin secretion is selective and was not observed in RINm5F cells ( , ). In the present studies, PTX did not inhibit the mastoparan-stimulated insulin release from cells overexpressing Cdc42.…”

Section: Discussionmentioning

confidence: 99%

“…Insulin release from the pancreatic β-cell is under the control of a variety of nutrient, hormone, and neurotransmitter signals that enhance or inhibit insulin release by complex mechanisms ( − ). Mastoparan, a toxin from wasp venom, can stimulate exocytosis in a number of mammalian cells including pancreatic β-cells ( − ). While the mechanism of stimulation of insulin release is unclear, the effect of mastoparan appears to be independent of the requirement for [Ca 2+ ] i ().…”

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confidence: 99%

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A Link between Cdc42 and Syntaxin Is Involved in Mastoparan-Stimulated Insulin Release

et al. 2002

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Mastoparan, a hormone receptor-mimetic peptide isolated from wasp venom, stimulates insulin release from pancreatic beta-cells in a Ca(2+)-independent but GTP-dependent manner. In this report, the role of the Rho family GTP-binding protein Cdc42, in the mastoparan stimulus-secretion pathway, was examined. Overexpression of wild-type Cdc42 in beta HC-9 cells, an insulin-secreting mouse-derived cell line, resulted in a 2-fold increase in mastoparan-stimulated insulin release over vector-transfected beta HC-9 cells. This effect was not seen with secretagogues such as glucose that stimulate secretion via Ca(2+)-dependent pathways. GDP/GTP exchange assay data and studies with pertussis (PTX) toxin suggest that mastoparan may work directly to activate Cdc42 and not via PTX-sensitive heterotrimeric GTP-binding proteins. Using bacterial glutathione S-transferase-Cdc42 fusion proteins and co-immunoprecipitation and transient transfection studies, Cdc42 was shown to be an upstream regulator of the exocytotic protein, syntaxin. These results suggest that the GTP-dependent signal underlying the mastoparan effect acts at a "distal site" in stimulus-secretion coupling on one of the SNARE proteins essential for exocytosis. In vitro binding assays, using purified Cdc42 and syntaxin proteins, show that Cdc42 mediates the GTP signal through an indirect association with syntaxin. The H3 domain at the C-terminus of syntaxin, which participates in the formation of the ternary SNARE complex with the core proteins, SNAP-25 and synaptobrevin, is also required for the association with Cdc42. Thus, these studies indicate that Cdc42 could be a putative GTP-binding protein thought to be involved in the mastoparan-stimulated GTP-dependent pathway of insulin release.

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“…Έχει αναφερθεί ότι το μαστοπαράν, ένα τετραδεκαπεπτίδιο από το δηλητήριο της σφήκας(Hagashijima et al, 1990), ενεργοποιεί την καταλυτική καθώς και τη φωσφοενζυμική διαμόρφωση της NDP κινάσης στο κυτταρόπλασμα ηπατικών κυττάρων του αρουραίου(Kikkawa et al, 1992). Σε μελέτες άλλων εργαστηρίων(Jones et al, 1993;Komatsu et al, 1993;Metz et al, 1993b) έχει διαπιστωθεί ότι το μαστοπαράν ενεργοποιεί την έκκριση ινσουλίνης από μεμονωμένα νησίδια όπως και από καθαρά β-κύτταρα μέσω ενός μηχανισμού που δεν είναι γνωστός. Επιπλέον παρατηρήθηκε ότι αυτό το πεπτίδιο σε συγκεντρώσεις (30μΜ) ενεργοποιούσε τη δράση της NDP κινάσης στα νησίδια.…”

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Καθαρισμός Ιδιότητες Και Εξειδίκευση Ισομορφών Κινασών Των Διφωσφονουκλεοζιτών Από Ενδοσπέρμιο Καλαμποκιού - Μοριακές Προσεγγίσεις

Βεργίδου¹

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Mastoparan stimulates exocytosis at a Ca(2+)-independent late site in stimulus-secretion coupling. Studies with the RINm5F beta-cell line.

Cited by 69 publications

References 49 publications

Characterization of Nucleoside Diphosphokinase Activity in Human and Rodent Pancreatic .beta. Cells: Evidence for Its Role in the Formation of Guanosine Triphosphate, a Permissive Factor for Nutrient-Induced Insulin Secretion

Characterization of Nucleoside Diphosphokinase Activity in Human and Rodent Pancreatic .beta. Cells: Evidence for Its Role in the Formation of Guanosine Triphosphate, a Permissive Factor for Nutrient-Induced Insulin Secretion

A Link between Cdc42 and Syntaxin Is Involved in Mastoparan-Stimulated Insulin Release

Καθαρισμός Ιδιότητες Και Εξειδίκευση Ισομορφών Κινασών Των Διφωσφονουκλεοζιτών Από Ενδοσπέρμιο Καλαμποκιού - Μοριακές Προσεγγίσεις

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