Cookies Notification

We use cookies to improve your website experience. To learn about our use of cookies and how you can manage your cookie settings, please see our Cookie Policy.
×

Palmitoylation of prohibitin at cysteine 69 facilitates its membrane translocation and interaction with Eps 15 homology domain protein 2 (EHD2)

Publication: Biochemistry and Cell Biology
18 May 2010

Abstract

Plasma membrane translocation of specific cytosolic proteins plays an important role in cell signaling pathways. We have recently shown that prohibitin (PHB), a protein present in the plasma membranes of various cell types, interacts with Eps 15 homology domain protein 2 (EHD2), a lipid raft protein. However, the mechanism involved in membrane translocation of PHB is not known.We report that PHB undergoes palmitoylation at cysteine 69 (Cys69), and that this palmitoylation is required for PHB's membrane translocation. Furthermore, we demonstrate that membrane translocation of PHB facilitates tyrosine phosphorylation and its interaction with EHD2. Thus, the palmitoylation and membrane translocation of PHB and its interaction with EHD2 may play a role in cell signaling.

Résumé

La translocation de protéines cytosoliques spécifiques à travers la membrane plasmique joue un rôle important dans les voies de signalisation cellulaire. La prohibitine (PHB) est présente dans la membrane plasmique des plusieurs types de cellules et récemment, nous avons démontré que la PHB interagissait avec la protéine EHD2 (« Eps 15 homology domain protein 2 »), une protéine des radeaux lipidiques. Par ailleurs, le mécanisme impliqué dans la translocation membranaire de la PHB n’est pas connu. Nous rapportons ici que la PHB subit une palmitoylation sur la cystéine 69 (Cys69) et que la palmitoylation est requise à la translocation membranaire de la PHB. De plus, nous démontrons que la translocation membranaire de la PHB facilite sa phosphorylation sur tyrosine et son interaction avec l’EDH2. La palmitoylation et la translocation membranaire de la PHB et son interaction avec l’EDH2 pourraient jouer un rôle dans la signalisation cellulaire.

Get full access to this article

View all available purchase options and get full access to this article.

References

Ande, S.R., Gu, Y., Nyomba, B.L.G., and Mishra, S. 2009. Insulin induced phosphorylation of prohibitin at Tyrosine 114 recruits Shp1. Biochim. Biophys. Acta, 1793(8): 1372–1378.
Baumann, C.A., Ribon, V., Kanzaki, M., Thurmond, D.C., Mora, S., Shigematsu, S., et al. 2000. CAP defines a second signaling pathway required for insulin-stimuated glucose transport. Nature, 407(6801): 147–148.
Bickel, P.E. 2002. Lipid rafts and insulin signaling. Am. J. Physiol. Endocrinol. Metab. 282(1): E1–E10.
Guilherme, A., Soriano, N.A., Bose, S., Holik, J., Bose, A., Pomerleau, D.P., et al. 2004a. EHD2 and the novel EH domain binding protein EHBP1 couple endocytosis to the actin cytoskeleton. J. Biol. Chem. 279(11): 10593–10605.
Guilherme, A., Soriano, N.A., Furcinitti, P.S., and Czech, M.P. 2004b. Role of EHD1 and EHBP1 in perinuclear sorting and insulin-regulated GLUT4 recycling in 3T3-L1 adipocytes. J. Biol. Chem. 279(38): 40062–40075.
Huber, T.B., Schermer, B., Müller, R.U., Höhne, M., Bartram, M., Calixto, A., et al. 2006. Podocin and MEC-2 bind cholesterol to regulate the activity of associated ion channels. Proc. Natl. Acad. Sci. U.S.A. 103(46): 17079–17086.
Inokuchi, J. 2006. Insulin resistance is a membrane microdomain disorder. Biol. Pharm. Bull. 29(8): 1532–1537.
Kanaani, J., Diacovo, M.J., El-Husseini, A.-D., Bredt, D.S., and Baekkeskov, S. 2004. Palmitoylation controls trafficking of GAD65 from Golgi membranes to axon-specific endosomes and a Rab5a-dependent pathway to presynaptic clusters. J. Cell Sci. 117(Pt 10): 2001–2013.
Kolonin, M.G., Saha, P.K., Chan, L., Pasqualini, R., and Arap, W. 2004. Reversal of obesity by targeted ablation of adipose tissue. Nat. Med. 10(6): 625–632.
Mayer, B.J. 1999. Endocytosis: EH domains lend a hand. Curr. Biol. 9(2): R70–R73.
Mielenz, D., Vettermann, C., Hampel, M., Lang, C., Avramidou, A., Karas, M., and Jäck, H.M. 2005. Lipid rafts associate with intracellular B cell receptors and exhibit a B cell stage-specific protein composition. J. Immunol. 174(6): 3508–3517.
Mishra, S., Murphy, L.C., Nyomba, B.L.G., and Murphy, L.J. 2005. Prohibitin: a potential target for new therapeutics. Trends Mol. Med. 11(4): 192–197.
Mishra, S., Murphy, L.C., and Murphy, L.J. 2006. The Prohibitins: emerging roles in diverse functions. J. Cell. Mol. Med. 10(2): 353–363.
Mishra, S., Melino, G., and Murphy, L.J. 2007. Transglutaminase 2 kinase activity facilitates protein kinase A-induced phosphorylation of retinoblastoma protein. J. Biol. Chem. 282(25): 18108–18115.
Morrow, I.C., and Parton, R.G. 2005. Flotillins and the PHB domain protein family: rafts, worms and anaesthetics. Traffic, 6(9): 725–740.
Morrow, I.C., Rea, S., Martin, S., Prior, I.A., Prohaska, R., Hancock, J.F., et al. 2002. Flotillin-1/reggie-2 traffics to surface raft domains via a novel golgi-independent pathway. Identification of a novel membrane targeting domain and a role for palmitoylation. J. Biol. Chem. 277(50): 48834–48841.
Park, S.Y., Ha, B.G., Choi, G.H., Ryu, J., Kim, B., Jung, C.Y., and Lee, W. 2004. EHD2 interacts with the insulin-responsive glucose transporter (GLUT4) in rat adipocytes and may participate in insulin-induced GLUT4 recruitment. Biochemistry, 43(23): 7552–7562.
Rajalingam, K., Wunder, C., Brinkmann, V., Churin, Y., Hekman, M., Sievers, C., et al. 2005. Prohibitin is required for Ras-induced Raf-MEK-ERK activation and epithelial cell migration. Nat. Cell Biol. 7(8): 837–843.
Resh, M.D. 2004. Membrane targeting of lipid modified signal transduction proteins. Subcell. Biochem. 37: 217–232.
Resh, M.D. 2006. Palmitoylation of ligands, receptors, and intracellular signaling molecules. Sci. STKE, 2006(359): re14.
Santolini, E., Salcini, A.E., Kay, B.K., Yamabhai, M., and Di Fiore, P.P. 1999. The EH network. Exp. Cell Res. 253(1): 186–209.
Schmidt, C., Kim, D., Ippolito, G.C., Naqvi, H.R., Probst, L., Mathur, S., et al. 2009. Signalling of the BCR is regulated by a lipid rafts-localised transcription factor, Bright. EMBO J. 28(6): 711–724.
Sharma, A., and Qadri, A. 2004. Vi polysaccharide of Salmonella typhi targets the prohibitin family of molecules in intestinal epithelial cells and suppresses early inflammatory responses. Proc. Natl. Acad. Sci. U.S.A. 101(50): 17492–17497.
Snyers, L., Umlauf, E., and Prohaska, R. 1999. Cysteine 29 is the major palmitoylation site on stomatin. FEBS Lett. 449(2-3): 101–104.
Terashima, M., Kim, K.M., Adachi, T., Nielsen, P.J., Reth, M., Köhler, G., and Lamers, M.C. 1994. The IgM antigen receptor of B lymphocytes is associated with prohibitin and a prohibitin-related protein. EMBO J. 13(16): 3782–3792.
Vessal, M., Mishra, S., Moulik, S., and Murphy, L.J. 2006. Prohibitin attenuates insulin-stimulated glucose and fatty acid oxidation in adipose tissue by inhibition of pyruvate carboxylase. FEBS J. 273(3): 568–576.

Information & Authors

Information

Published In

cover image Biochemistry and Cell Biology
Biochemistry and Cell Biology
Volume 88Number 3June 2010
Pages: 553 - 558

History

Received: 29 August 2009
Revision received: 17 November 2009
Accepted: 19 November 2009
Version of record online: 18 May 2010

Permissions

Request permissions for this article.

Key Words

  1. lipid rafts
  2. insulin signaling
  3. tyrosine phosphorylation
  4. protein–protein interaction
  5. S-acylation

Mots-clés

  1. radeaux lipidiques
  2. signalisation de l’insuline
  3. phosphorylation sur tyrosine
  4. interaction protéine–protéine
  5. S-acylation

Authors

Affiliations

Sudharsana Rao Ande
Department of Internal Medicine, University of Manitoba, 843 John Buhler Research Centre, 715 McDermot Ave., Winnipeg, MB R3E 3P4, Canada.
Department of Internal Medicine, University of Manitoba, 843 John Buhler Research Centre, 715 McDermot Ave., Winnipeg, MB R3E 3P4, Canada.

Metrics & Citations

Metrics

Other Metrics

Citations

Cite As

Export Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

Cited by

1. Prohibitin-1 is an ACTH-Regulated Protein in Human and Mouse Adrenocortical Cells and Plays a Role in Corticosteroid Production
2. Prohibitin plays a role in the functional plasticity of macrophages
3. Fatty acid mobilization from adipose tissue is mediated by CD36 posttranslational modifications and intracellular trafficking
4. Prohibitin ligands: a growing armamentarium to tackle cancers, osteoporosis, inflammatory, cardiac and neurological diseases
5. Function of Platelet Glycosphingolipid Microdomains/Lipid Rafts
6. Prohibitin 1 in liver injury and cancer
7.
8. Characterization and functionality of two members of the SPFH protein superfamily, prohibitin 1 and 2 in Leishmania major
9. Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies
10. Prohibitin: a potential therapeutic target in tyrosine kinase signaling
11. Targeting prohibitins with chemical ligands inhibits KRAS-mediated lung tumours
12. Prohibitin – At the crossroads of obesity-linked diabetes and cancer
13. The Scaffold Protein Prohibitin Is Required for Antigen-Stimulated Signaling in Mast Cells
14. A Role for Prohibitin in Mast Cell Activation: Location Matters
15. Prohibitin Ligands in Cell Death and Survival: Mode of Action and Therapeutic Potential
16. Raf activation by Ras and promotion of cellular metastasis require phosphorylation of prohibitin in the raft domain of the plasma membrane
17. Signaling pathways of prohibitin and its role in diseases
18. Proteomic analysis of UVB-induced protein expression- and redox-dependent changes in skin fibroblasts using lysine- and cysteine-labeling two-dimensional difference gel electrophoresis
19. EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization
20. Mitochondrial–Nuclear Communication by Prohibitin Shuttling under Oxidative Stress
21. Proteomic profiling of lipid rafts in a human breast cancer model of tumorigenic progression
22. EHD proteins: key conductors of endocytic transport
23. The role of prohibitin in cell signaling

View Options

Get Access

Login options

Check if you access through your login credentials or your institution to get full access on this article.

Subscribe

Click on the button below to subscribe to Biochemistry and Cell Biology

Purchase options

Purchase this article to get full access to it.

Restore your content access

Enter your email address to restore your content access:

Note: This functionality works only for purchases done as a guest. If you already have an account, log in to access the content to which you are entitled.

View options

PDF

View PDF

Full Text

View Full Text

Media

Media

Other

Tables

Share Options

Share

Share the article link

Share on social media