Cyclin-dependent kinase 5 associated with p39 promotes Munc18-1 phosphorylation and Ca2+-dependent exocytosis

Lena Lilja, Jenny Ulrika Johansson, Jesper Gromada, Slavena Andrea Mandic, Gabriel Fried, Per Olof Berggren, Christina Bark

Research output: Contribution to journalArticle

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Abstract

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine protein kinase that requires association with a regulatory protein, p35 or p39, to form an active enzyme. Munc18-1 plays an essential role in membrane fusion, and its function is regulated by phosphorylation. We report here that both p35 and p39 were expressed in insulin-secreting β-cells, where they exhibited individual subcellular distributions and associated with membranous organelles of different densities. Overexpression of Cdk5, p35, or p39 showed that Cdk5 and p39 augmented Ca2+-induced insulin exocytosis. Suppression of p39 and Cdk5, but not of p35, by antisense oligonucleotides selectively inhibited insulin exocytosis. Transient transfection of primary β-cells with Munc18-1 templates mutated in potential Cdk5 or PKC phosphorylation sites, in combination with Cdk5 and the different Cdk5 activators, suggested that Cdk5/p39-promoted Ca2+-dependent insulin secretion from primary β-cells by phosphorylating Munc18-1 at a biochemical step immediately prior to vesicle fusion.

Original languageEnglish
Pages (from-to)29534-29541
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number28
DOIs
StatePublished - Jul 9 2004
Externally publishedYes

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Cyclin-Dependent Kinase 5
Phosphorylation
Exocytosis
Insulin
Proline-Directed Protein Kinases
Fusion reactions
Membrane Fusion
Antisense Oligonucleotides
Protein-Serine-Threonine Kinases
Insulin-Secreting Cells
Proline
Organelles
Transfection
Association reactions
Membranes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Lilja, L., Johansson, J. U., Gromada, J., Mandic, S. A., Fried, G., Berggren, P. O., & Bark, C. (2004). Cyclin-dependent kinase 5 associated with p39 promotes Munc18-1 phosphorylation and Ca2+-dependent exocytosis. Journal of Biological Chemistry, 279(28), 29534-29541. https://doi.org/10.1074/jbc.M312711200

Cyclin-dependent kinase 5 associated with p39 promotes Munc18-1 phosphorylation and Ca2+-dependent exocytosis. / Lilja, Lena; Johansson, Jenny Ulrika; Gromada, Jesper; Mandic, Slavena Andrea; Fried, Gabriel; Berggren, Per Olof; Bark, Christina.

In: Journal of Biological Chemistry, Vol. 279, No. 28, 09.07.2004, p. 29534-29541.

Research output: Contribution to journalArticle

Lilja, L, Johansson, JU, Gromada, J, Mandic, SA, Fried, G, Berggren, PO & Bark, C 2004, 'Cyclin-dependent kinase 5 associated with p39 promotes Munc18-1 phosphorylation and Ca2+-dependent exocytosis', Journal of Biological Chemistry, vol. 279, no. 28, pp. 29534-29541. https://doi.org/10.1074/jbc.M312711200
Lilja, Lena ; Johansson, Jenny Ulrika ; Gromada, Jesper ; Mandic, Slavena Andrea ; Fried, Gabriel ; Berggren, Per Olof ; Bark, Christina. / Cyclin-dependent kinase 5 associated with p39 promotes Munc18-1 phosphorylation and Ca2+-dependent exocytosis. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 28. pp. 29534-29541.
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