Biopolym. Cell. 2006; 22(3):217-224.
Molecular Mechanisms of Differentiation
Interaction of fatty acid transporting protein FABP4 with phosphatase PTEN
1Gorbenko O. M., 2Panayotou G., 1Volkova D. D., 1Zhyvoloup O. M., 1Kukharenko O. P., 1, 3Gout I. T., 1Filonenko V. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Biomedical Sciences Research Center "Alexander Fleming"
    34 Fleming Str., 16672, Vari, Greece
  3. Research Department of Structural and Molecular Biology, University College London
    Gower Str., London WC1E 6BT, UK

Abstract

PTEN is a tumour suppressor protein with dual protein and lipid phosphatase activity, which is frequently deleted or mutated in many advanced cancers. At least 20 % of its mutations are found in C-terminal domain of the phosphatase. Recent studies show that PTEN also plays an important role in the development of insulin resistance and glucose tolerance, thus it may be an important target in the diabetes 2 type and atherosclerosis treatment. Using C-terminal fragment of PTEN as a bait in yeast two-hybrid screening cDNA library of 18-day mouse embryo a novel PTEN binding protein –FABP4, which is a marker of adipocyte differentiation, has been identified. PTEN-FABP4 interaction was confirmed by mating assay, in vitro pull-down assay and BIAcore analysis. Our results show that PTEN phosphatase may be involved into regulation of adipose tissue formation through the interaction with fatty acid transporter FABP4.
Keywords: PTEN phosphatase, FABP4, lipid metabolism

References

[1] Goberdhan DC, Wilson C. PTEN: tumour suppressor, multifunctional growth regulator and more. Hum Mol Genet. 2003;12 Spec No 2:R239-48.
[2] Simpson L, Parsons R. PTEN: life as a tumor suppressor. Exp Cell Res. 2001;264(1):29-41.
[3] Eng C. PTEN: one gene, many syndromes. Hum Mutat. 2003;22(3):183-98.
[4] Marsh DJ, Coulon V, Lunetta KL, Rocca-Serra P, Dahia PL, Zheng Z, Liaw D, Caron S, Dubou? B, Lin AY, Richardson AL, Bonnetblanc JM, Bressieux JM, Cabarrot-Moreau A, Chompret A, Demange L, Eeles RA, Yahanda AM, Fearon ER, Fricker JP, Gorlin RJ, Hodgson SV, Huson S, Lacombe D, Eng C, et al. Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum Mol Genet. 1998;7(3):507-15.
[5] Myers MP, Pass I, Batty IH, Van der Kaay J, Stolarov JP, Hemmings BA, Wigler MH, Downes CP, Tonks NK. The lipid phosphatase activity of PTEN is critical for its tumor supressor function. Proc Natl Acad Sci U S A. 1998;95(23):13513-8.
[6] Suzuki A, de la Pompa JL, Stambolic V, Elia AJ, Sasaki T, del Barco Barrantes I, Ho A, Wakeham A, Itie A, Khoo W, Fukumoto M, Mak TW. High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol. 1998;8(21):1169-78.
[7] Stiles B, Wang Y, Stahl A, Bassilian S, Lee WP, Kim YJ, Sherwin R, Devaskar S, Lesche R, Magnuson MA, Wu H. Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity [corrected]. Proc Natl Acad Sci U S A. 2004;101(7):2082-7.
[8] Wijesekara N, Konrad D, Eweida M, Jefferies C, Liadis N, Giacca A, Crackower M, Suzuki A, Mak TW, Kahn CR, Klip A, Woo M. Muscle-specific Pten deletion protects against insulin resistance and diabetes. Mol Cell Biol. 2005;25(3):1135-45.
[9] Kurlawalla-Martinez C, Stiles B, Wang Y, Devaskar SU, Kahn BB, Wu H. Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue. Mol Cell Biol. 2005;25(6):2498-510.
[10] Chen XD, Lei T, Xia T, Gan L, Yang ZQ. Increased expression of resistin and tumour necrosis factor-alpha in pig adipose tissue as well as effect of feeding treatment on resistin and cAMP pathway. Diabetes Obes Metab. 2004;6(4):271-9.
[11] Maehama T, Dixon JE. PTEN: a tumour suppressor that functions as a phospholipid phosphatase. Trends Cell Biol. 1999;9(4):125-8.
[12] Sun H, Lesche R, Li DM, Liliental J, Zhang H, Gao J, Gavrilova N, Mueller B, Liu X, Wu H. PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway. Proc Natl Acad Sci U S A. 1999;96(11):6199-204.
[13] Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, Ruland J, Penninger JM, Siderovski DP, Mak TW. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell. 1998;95(1):29-39.
[14] Tamura M, Gu J, Danen EH, Takino T, Miyamoto S, Yamada KM. PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway. J Biol Chem. 1999;274(29):20693-703.
[15] Gu J, Tamura M, Pankov R, Danen EH, Takino T, Matsumoto K, Yamada KM. Shc and FAK differentially regulate cell motility and directionality modulated by PTEN. J Cell Biol. 1999;146(2):389-403.
[16] Al-Khouri AM, Ma Y, Togo SH, Williams S, Mustelin T. Cooperative phosphorylation of the tumor suppressor phosphatase and tensin homologue (PTEN) by casein kinases and glycogen synthase kinase 3beta. J Biol Chem. 2005;280(42):35195-202.
[17] Okahara F, Ikawa H, Kanaho Y, Maehama T. Regulation of PTEN phosphorylation and stability by a tumor suppressor candidate protein. J Biol Chem. 2004;279(44):45300-3.
[18] Valiente M, Andr?s-Pons A, Gomar B, Torres J, Gil A, Tapparel C, Antonarakis SE, Pulido R. Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine. threonine kinases. J Biol Chem. 2005;280(32):28936-43.
[19] Wu X, Hepner K, Castelino-Prabhu S, Do D, Kaye MB, Yuan XJ, Wood J, Ross C, Sawyers CL, Whang YE. Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2. Proc Natl Acad Sci U S A. 2000;97(8):4233-8.
[20] Wu Y, Dowbenko D, Spencer S, Laura R, Lee J, Gu Q, Lasky LA. Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase. J Biol Chem. 2000;275(28):21477-85.
[21] Gorbenko O, Kuznetsov V, Kukharenko O, Zhyvoloup A, Panasyuk G, Nemazanyy I, Filonenko V, Gout I. Identification of a novel binding partners for tumor suppressor PTEN by a yeast two-hybrid approach. Eksp Onkol. 2004;26(1):15-9.
[22] Muise AM, Ro HS. Enzymic characterization of a novel member of the regulatory B-like carboxypeptidase with transcriptional repression function: stimulation of enzymic activity by its target DNA. Biochem J. 1999;343 Pt 2:341-5.
[23] Zhang L, Reidy SP, Nicholson TE, Lee HJ, Majdalawieh A, Webber C, Stewart BR, Dolphin P, Ro HS. The role of AEBP1 in sex-specific diet-induced obesity. Mol Med. 2005;11(1-12):39-47.
[24] Gorbenko O, Filonenko V, Gout I. Generation and characterization of monoclonal antibodies against FABP4. Hybridoma (Larchmt). 2006;25(2):86-90.
[25] J?nsson U, F?gerstam L, Ivarsson B, Johnsson B, Karlsson R, Lundh K, L?f?s S, Persson B, Roos H, R?nnberg I, et al. Real-time biospecific interaction analysis using surface plasmon resonance and a sensor chip technology. Biotechniques. 1991;11(5):620-7.
[26] Xu ZH, Buelt MK, Banaszak LJ, Bernlohr DA. Expression, purification, and crystallization of the adipocyte lipid binding protein. J Biol Chem. 1991;266(22):14367-70.
[27] Fu Y, Luo N, Lopes-Virella MF, Garvey WT. The adipocyte lipid binding protein (ALBP/aP2) gene facilitates foam cell formation in human THP-1 macrophages. Atherosclerosis. 2002;165(2):259-69.
[28] Fisher RM, Th?rne A, Hamsten A, Arner P. Fatty acid binding protein expression in different human adipose tissue depots in relation to rates of lipolysis and insulin concentration in obese individuals. Mol Cell Biochem. 2002;239(1-2):95-100.
[29] Amri EZ, Bertrand B, Ailhaud G, Grimaldi P. Regulation of adipose cell differentiation. I. Fatty acids are inducers of the aP2 gene expression. J Lipid Res. 1991;32(9):1449-56.
[30] Jenkins-Kruchten AE, Bennaars-Eiden A, Ross JR, Shen WJ, Kraemer FB, Bernlohr DA. Fatty acid-binding protein-hormone-sensitive lipase interaction. Fatty acid dependence on binding. J Biol Chem. 2003;278(48):47636-43.
[31] Hresko RC, Hoffman RD, Flores-Riveros JR, Lane MD. Insulin receptor tyrosine kinase-catalyzed phosphorylation of 422(aP2) protein. Substrate activation by long-chain fatty acid. J Biol Chem. 1990;265(34):21075-85.
[32] Scheja L, Makowski L, Uysal KT, Wiesbrock SM, Shimshek DR, Meyers DS, Morgan M, Parker RA, Hotamisligil GS. Altered insulin secretion associated with reduced lipolytic efficiency in aP2-/- mice. Diabetes. 1999;48(10):1987-94.
[33] Butler M, McKay RA, Popoff IJ, Gaarde WA, Witchell D, Murray SF, Dean NM, Bhanot S, Monia BP. Specific inhibition of PTEN expression reverses hyperglycemia in diabetic mice. Diabetes. 2002;51(4):1028-34.
[34] Horie Y, Suzuki A, Kataoka E, Sasaki T, Hamada K, Sasaki J, Mizuno K, Hasegawa G, Kishimoto H, Iizuka M, Naito M, Enomoto K, Watanabe S, Mak TW, Nakano T. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J Clin Invest. 2004;113(12):1774-83.
[35] Buelt MK, Shekels LL, Jarvis BW, Bernlohr DA. In vitro phosphorylation of the adipocyte lipid-binding protein (p15) by the insulin receptor. Effects of fatty acid on receptor kinase and substrate phosphorylation. J Biol Chem. 1991;266(19):12266-71.
[36] Buelt MK, Xu Z, Banaszak LJ, Bernlohr DA. Structural and functional characterization of the phosphorylated adipocyte lipid-binding protein (pp15). Biochemistry. 1992;31(13):3493-9.