help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ikonomov, O. C.
Right arrow Articles by Shisheva, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ikonomov, O. C.
Right arrow Articles by Shisheva, A.
Endocrinology Vol. 143, No. 12 4742-4754
Copyright © 2002 by The Endocrine Society

ARTICLE

Requirement for PIKfyve Enzymatic Activity in Acute and Long-Term Insulin Cellular Effects

Ognian C. Ikonomov, Diego Sbrissa, Krzysztof Mlak and Assia Shisheva

Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201

Address all correspondence and requests for reprints to: Assia Shisheva, Department of Physiology, Wayne State University School of Medicine, 540 East Canfield, Detroit, Michigan 48201. E-mail: ashishev{at}med.wayne.edu.

PIKfyve is a phosphoinositide 5-kinase that can also act as a protein kinase. PIKfyve’s role in acute insulin action has been suggested on the basis of its association with the insulin stimulatable phosphatidylinositol-3-kinase and the ability of acute insulin to recruit and phosphorylate PIKfyve on intracellular membranes of 3T3-L1 adipocytes. Here we have examined several classical insulin-regulated long- and short-term responses in insulin-sensitive cells expressing high levels of either active PIKfyve or kinase-dead mutants with a dominant-negative effect. Up-regulation of PIKfyve protein expression was documented in the early stages of differentiation of cultured 3T3-L1 fibroblasts into adipocytes and a kinase-dead mutant, PIKfyve{Delta}K, introduced into the preadipocyte stage profoundly delayed the hormone-induced adipogenesis. Next, insulin-induced mitogenesis was markedly inhibited in HEK293 stable cell lines, inducibly expressing the dominant-negative kinase-dead PIKfyveK1831E mutant but not in cells expressing PIKfyveWT. Similarly, expression of the dominant negative mutants PIKfyveK1831E or PIKfyve{Delta}K strongly inhibited insulin-stimulated translocation of GLUT4 in 3T3-L1 adipocytes, or GLUT1-mediated glucose uptake in Chinese hamster ovary T cells expressing the human insulin receptor. Expression of PIKfyve{Delta}K and PIKfyveWT in Chinese hamster ovary T cells decreased or increased, respectively, insulin-stimulated Akt phosphorylation at Ser473 but not at Thr308. Furthermore, a powerful inhibition of PIKfyve was documented at a very low concentration (ID50 = 6 µM) of the cell-permeable kinase inhibitor curcumin. When introduced into 3T3-L1 adipocytes, curcumin markedly inhibited insulin-induced GLUT4 translocation and glucose transport. Together these data indicate that PIKfyve enzymatic activity functions as a positive regulatory intermediate in insulin acute and long-term biological responses and identify Ser473 in Akt as one potential PIKfyve downstream target.




This article has been cited by other articles:


Home page
 J EndocrinolHome page
S. E Leney and J. M Tavare
The molecular basis of insulin-stimulated glucose uptake: signalling, trafficking and potential drug targets
J. Endocrinol., October 1, 2009; 203(1): 1 - 18.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. C. Ikonomov, D. Sbrissa, T. Ijuin, T. Takenawa, and A. Shisheva
Sac3 Is an Insulin-regulated Phosphatidylinositol 3,5-Bisphosphate Phosphatase: GAIN IN INSULIN RESPONSIVENESS THROUGH Sac3 DOWN-REGULATION IN ADIPOCYTES
J. Biol. Chem., September 4, 2009; 284(36): 23961 - 23971.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. C. Ikonomov, J. Fligger, D. Sbrissa, R. Dondapati, K. Mlak, R. Deeb, and A. Shisheva
Kinesin Adapter JLP Links PIKfyve to Microtubule-based Endosome-to-Trans-Golgi Network Traffic of Furin
J. Biol. Chem., February 6, 2009; 284(6): 3750 - 3761.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. Shisheva
Phosphoinositides in insulin action on GLUT4 dynamics: not just PtdIns(3,4,5)P3
Am J Physiol Endocrinol Metab, September 1, 2008; 295(3): E536 - E544.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. L. Osborne, P. J. Wen, C. Boucheron, H. N. Nguyen, M. Hayakawa, H. Kaizawa, P. J. Parker, N. Vitale, and F. A. Meunier
PIKfyve Negatively Regulates Exocytosis in Neurosecretory Cells
J. Biol. Chem., February 1, 2008; 283(5): 2804 - 2813.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. Yu, P.-O. Berggren, and C. J. Barker
An Autocrine Insulin Feedback Loop Maintains Pancreatic {beta}-Cell 3-Phosphorylated Inositol Lipids
Mol. Endocrinol., November 1, 2007; 21(11): 2775 - 2784.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Sbrissa, O. C. Ikonomov, Z. Fu, T. Ijuin, J. Gruenberg, T. Takenawa, and A. Shisheva
Core Protein Machinery for Mammalian Phosphatidylinositol 3,5-Bisphosphate Synthesis and Turnover That Regulates the Progression of Endosomal Transport: NOVEL SAC PHOSPHATASE JOINS THE ArPIKfyve-PIKfyve COMPLEX
J. Biol. Chem., August 17, 2007; 282(33): 23878 - 23891.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
F. S. L. Thong, C. B. Dugani, and A. Klip
Turning Signals On and Off: GLUT4 Traffic in the Insulin-Signaling Highway
Physiology, August 1, 2005; 20(4): 271 - 284.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Kalant, R. MacLaren, W. Cui, R. Samanta, P. N. Monk, S. A. Laporte, and K. Cianflone
C5L2 Is a Functional Receptor for Acylation-stimulating Protein
J. Biol. Chem., June 24, 2005; 280(25): 23936 - 23944.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
D. C. Berwick, G. C. Dell, G. I. Welsh, K. J. Heesom, I. Hers, L. M. Fletcher, F. T. Cooke, and J. M. Tavare
Protein kinase B phosphorylation of PIKfyve regulates the trafficking of GLUT4 vesicles
J. Cell Sci., December 1, 2004; 117(25): 5985 - 5993.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. Sbrissa, O. C. Ikonomov, J. Strakova, and A. Shisheva
Role for a Novel Signaling Intermediate, Phosphatidylinositol 5-Phosphate, in Insulin-Regulated F-Actin Stress Fiber Breakdown and GLUT4 Translocation
Endocrinology, November 1, 2004; 145(11): 4853 - 4865.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. C. Ikonomov, D. Sbrissa, K. Mlak, R. Deeb, J. Fligger, A. Soans, R. L. Finley Jr., and A. Shisheva
Active PIKfyve Associates with and Promotes the Membrane Attachment of the Late Endosome-to-trans-Golgi Network Transport Factor Rab9 Effector p40
J. Biol. Chem., December 19, 2003; 278(51): 50863 - 50871.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Sbrissa, O. C. Ikonomov, R. Deeb, and A. Shisheva
Phosphatidylinositol 5-Phosphate Biosynthesis Is Linked to PIKfyve and Is Involved in Osmotic Response Pathway in Mammalian Cells
J. Biol. Chem., November 27, 2002; 277(49): 47276 - 47284.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2002 by The Endocrine Society