This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, M. Y. Articles by Walker, C. L. Search for Related Content PubMed PubMed Citation Articles by Liu, M. Y. Articles by Walker, C. L.

14-3-3 Interacts with the Tumor Suppressor Tuberin at Akt Phosphorylation Site(s)¹

Department of Carcinogenesis, Science Park-Research Division, The University of Texas M. D. Anderson Cancer Center, Smithville, Texas 78957

Tuberin, the product of the tuberous sclerosis complex 2 tumor suppressor gene, is a phosphoprotein that negatively regulates phosphatidylinositol 3'-kinase signaling downstream of Akt. Several high stringency 14-3-3 binding sites that overlapped with Akt phosphorylation sites were identified in tuberin in silico. Recognition of tuberin by an -14-3-3 binding site-specific antibody correlated with mitogen-induced phosphorylation of tuberin and recognition of tuberin by an -Akt phosphorylation substrate antibody. Recognition of tuberin by both antibodies was blocked by inhibiting phosphatidylinositol 3'-kinase activity. Using a protein domain microarray, a tuberin peptide containing Ser⁹³⁹ demonstrated phospho-specific binding to 14-3-3. Glutathione S-transferase pull-down assays with 14-3-3 fusion proteins revealed that all seven 14-3-3 isoforms (ß, , , , , , and ) could bind tuberin, and this interaction was abrogated by competition with phosphorylated but not unphosphorylated Ser⁹³⁹ tuberin peptide. Tuberin also coimmunoprecipitated with 14-3-3, confirming the interaction between endogenous 14-3-3 and tuberin. These data establish the presence of functional and overlapping 14-3-3 and Akt recognition site(s) in tuberin.

This article has been cited by other articles:

				A. J. Snow, P. Puri, A. Acker-Palmer, T. Bouwmeester, S. Vijayaraghavan, and D. Kline Phosphorylation-Dependent Interaction of Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein (YWHA) with PADI6 Following Oocyte Maturation in Mice Biol Reprod, August 1, 2008; 79(2): 337 - 347. [Abstract] [Full Text] [PDF]

				L. R. Jagemann, L. G. Perez-Rivas, E. J. Ruiz, J. A. Ranea, F. Sanchez-Jimenez, A. R. Nebreda, E. Alba, and J. Lozano The Functional Interaction of 14-3-3 Proteins with the ERK1/2 Scaffold KSR1 Occurs in an Isoform-specific Manner J. Biol. Chem., June 20, 2008; 283(25): 17450 - 17462. [Abstract] [Full Text] [PDF]

				T. Fan, R. Li, N. W. Todd, Q. Qiu, H.-B. Fang, H. Wang, J. Shen, R. Y. Zhao, N. P. Caraway, R. L. Katz, et al. Up-regulation of 14-3-3{zeta} in Lung Cancer and Its Implication as Prognostic and Therapeutic Target Cancer Res., August 15, 2007; 67(16): 7901 - 7906. [Abstract] [Full Text] [PDF]

				M. Rosner, A. Freilinger, M. Hanneder, N. Fujita, G. Lubec, T. Tsuruo, and M. Hengstschlager p27Kip1 localization depends on the tumor suppressor protein tuberin Hum. Mol. Genet., July 1, 2007; 16(13): 1541 - 1556. [Abstract] [Full Text] [PDF]

				S. C. Juvet, F. X. McCormack, D. J. Kwiatkowski, and G. P. Downey Molecular Pathogenesis of Lymphangioleiomyomatosis: Lessons Learned from Orphans Am. J. Respir. Cell Mol. Biol., April 1, 2007; 36(4): 398 - 408. [Abstract] [Full Text] [PDF]

				F. Vandermoere, I. E. Yazidi-Belkoura, Y. Demont, C. Slomianny, J. Antol, J. Lemoine, and H. Hondermarck Proteomics Exploration Reveals That Actin Is a Signaling Target of the Kinase Akt Mol. Cell. Proteomics, January 1, 2007; 6(1): 114 - 124. [Abstract] [Full Text] [PDF]

				X. Yang, W. H. Lee, F. Sobott, E. Papagrigoriou, C. V. Robinson, J. G. Grossmann, M. Sundstrom, D. A. Doyle, and J. M. Elkins Structural basis for protein-protein interactions in the 14-3-3 protein family PNAS, November 14, 2006; 103(46): 17237 - 17242. [Abstract] [Full Text] [PDF]

				P. B. Crino, K. L. Nathanson, and E. P. Henske The Tuberous Sclerosis Complex. N. Engl. J. Med., September 28, 2006; 355(13): 1345 - 1356. [Full Text] [PDF]

				N. J. Godde, G. M. D'Abaco, L. Paradiso, and U. Novak Efficient ADAM22 surface expression is mediated by phosphorylation-dependent interaction with 14-3-3 protein family members J. Cell Sci., August 15, 2006; 119(16): 3296 - 3305. [Abstract] [Full Text] [PDF]

				S.-L. Cai, A. R. Tee, J. D. Short, J. M. Bergeron, J. Kim, J. Shen, R. Guo, C. L. Johnson, K. Kiguchi, and C. L. Walker Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning J. Cell Biol., April 24, 2006; 173(2): 279 - 289. [Abstract] [Full Text] [PDF]

				K. Funai, J. D. Parkington, S. Carambula, and R. A. Fielding Age-associated decrease in contraction-induced activation of downstream targets of Akt/mTor signaling in skeletal muscle Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2006; 290(4): R1080 - R1086. [Abstract] [Full Text] [PDF]

				H. Liu, D. C. Radisky, C. M. Nelson, H. Zhang, J. E. Fata, R. A. Roth, and M. J. Bissell Mechanism of Akt1 inhibition of breast cancer cell invasion reveals a protumorigenic role for TSC2. PNAS, March 14, 2006; 103(11): 4134 - 4139. [Abstract] [Full Text] [PDF]

				A. D. Basso, P. Kirschmeier, and W. R. Bishop Thematic review series: Lipid Posttranslational Modifications. Farnesyl transferase inhibitors J. Lipid Res., January 1, 2006; 47(1): 15 - 31. [Abstract] [Full Text] [PDF]

				A. D. Basso, A. Mirza, G. Liu, B. J. Long, W. R. Bishop, and P. Kirschmeier The Farnesyl Transferase Inhibitor (FTI) SCH66336 (lonafarnib) Inhibits Rheb Farnesylation and mTOR Signaling: ROLE IN FTI ENHANCEMENT OF TAXANE AND TAMOXIFEN ANTI-TUMOR ACTIVITY J. Biol. Chem., September 2, 2005; 280(35): 31101 - 31108. [Abstract] [Full Text] [PDF]

				A. Benzinger, N. Muster, H. B. Koch, J. R. Yates III, and H. Hermeking Targeted Proteomic Analysis of 14-3-3{varsigma}, a p53 Effector Commonly Silenced in Cancer Mol. Cell. Proteomics, June 1, 2005; 4(6): 785 - 795. [Abstract] [Full Text] [PDF]

				N. Hay and N. Sonenberg Upstream and downstream of mTOR Genes & Dev., August 15, 2004; 18(16): 1926 - 1945. [Abstract] [Full Text] [PDF]

				M. Karbowniczek, T. Cash, M. Cheung, G. P. Robertson, A. Astrinidis, and E. P. Henske Regulation of B-Raf Kinase Activity by Tuberin and Rheb Is Mammalian Target of Rapamycin (mTOR)-independent J. Biol. Chem., July 16, 2004; 279(29): 29930 - 29937. [Abstract] [Full Text] [PDF]

				M. K. Dougherty and D. K. Morrison Unlocking the code of 14-3-3 J. Cell Sci., April 15, 2004; 117(10): 1875 - 1884. [Abstract] [Full Text] [PDF]

				J. Yu, A. Astrinidis, S. Howard, and E. P. Henske Estradiol and tamoxifen stimulate LAM-associated angiomyolipoma cell growth and activate both genomic and nongenomic signaling pathways Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L694 - L700. [Abstract] [Full Text] [PDF]

				A. Astrinidis, W. Senapedis, T. R. Coleman, and E. P. Henske Cell Cycle-regulated Phosphorylation of Hamartin, the Product of the Tuberous Sclerosis Complex 1 Gene, by Cyclin-dependent Kinase 1/Cyclin B J. Biol. Chem., December 19, 2003; 278(51): 51372 - 51379. [Abstract] [Full Text] [PDF]

				A. R. Tee, R. Anjum, and J. Blenis Inactivation of the Tuberous Sclerosis Complex-1 and -2 Gene Products Occurs by Phosphoinositide 3-Kinase/Akt-dependent and -independent Phosphorylation of Tuberin J. Biol. Chem., September 26, 2003; 278(39): 37288 - 37296. [Abstract] [Full Text] [PDF]

				V. P. Krymskaya and J. M. Shipley Lymphangioleiomyomatosis: A Complex Tale of Serum Response Factor-Mediated Tissue Inhibitor of Metalloproteinase-3 Regulation Am. J. Respir. Cell Mol. Biol., May 1, 2003; 28(5): 546 - 550. [Full Text] [PDF]

				Y. Li, K. Inoki, P. Vacratsis, and K.-L. Guan The p38 and MK2 Kinase Cascade Phosphorylates Tuberin, the Tuberous Sclerosis 2 Gene Product, and Enhances Its Interaction with 14-3-3 J. Biol. Chem., April 11, 2003; 278(16): 13663 - 13671. [Abstract] [Full Text] [PDF]