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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Phosphorylation of REPS1 at Ser709 by RSK attenuates the recycling of transferrin receptor

  • Kim, Seong Heon (Department of Functional Genomics, KRIBB School of Biological Science, Korea University of Science and Technology) ;
  • Cho, Jin-hwa (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Bi-Oh (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Byoung Chul (Department of Functional Genomics, KRIBB School of Biological Science, Korea University of Science and Technology) ;
  • Kim, Jeong-Hoon (Department of Functional Genomics, KRIBB School of Biological Science, Korea University of Science and Technology) ;
  • Park, Sung Goo (Department of Functional Genomics, KRIBB School of Biological Science, Korea University of Science and Technology) ;
  • Kim, Sunhong (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2020.12.02
  • Accepted : 2020.12.24
  • Published : 2021.05.31
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Abstract

RalBP1 associated EPS domain containing 1 (REPS1) is conserved from Drosophila to humans and implicated in the endocytic system. However, an exact role of REPS1 remains largely unknown. Here, we demonstrated that mitogen activated protein kinase kinase (MEK)-p90 ribosomal S6 Kinase (RSK) signaling pathway directly phosphorylated REPS1 at Ser709 upon stimulation by epidermal growth factor (EGF) and amino acid. While REPS2 is known to be involved in the endocytosis of EGF receptor (EGFR), REPS1 knockout (KO) cells did not show any defect in the endocytosis of EGFR. However, in the REPS1 KO cells and the KO cells reconstituted with a non-phosphorylatable REPS1 (REPS1 S709A), the recycling of transferrin receptor (TfR) was attenuated compared to the cells reconstituted with wild type REPS1. Collectively, we suggested that the phosphorylation of REPS1 at S709 by RSK may have a role of the trafficking of TfR.

Keywords

Acknowledgement

This work was supported by a grant (CAP-15-11-KRICT) from the National Research Council of Science and Technology, Ministry of Science, ICT, and Future Planning, a grant (NRF-2019M3E5D4069882) from the National Research Foundation, Ministry of Science and ICT and Future Planning, and a grant from the KRIBB Initiative Program.

References

  1. Levkowitz G, Waterman H, Ettenberg SA et al (1999) Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Mol Cell 4, 1029-1040 https://doi.org/10.1016/S1097-2765(00)80231-2
  2. Ettenberg SA, Keane MM, Nau MM et al (1999) cbl-b inhibits epidermal growth factor receptor signaling. Oncogene 18, 1855-1866 https://doi.org/10.1038/sj.onc.1202499
  3. Biscardi JS, Maa MC, Tice DA, Cox ME, Leu TH and Parsons SJ (1999) c-Src-mediated phosphorylation of the epidermal growth factor receptor on Tyr845 and Tyr1101 is associated with modulation of receptor function. J Biol Chem 274, 8335-8343 https://doi.org/10.1074/jbc.274.12.8335
  4. Emlet DR, Moscatello DK, Ludlow LB and Wong AJ (1997) Subsets of epidermal growth factor receptors during activation and endocytosis. J Biol Chem 272, 4079-4086 https://doi.org/10.1074/jbc.272.7.4079
  5. Rojas M, Yao S and Lin YZ (1996) Controlling epidermal growth factor (EGF)-stimulated Ras activation in intact cells by a cell-permeable peptide mimicking phosphorylated EGF receptor. J Biol Chem 271, 27456-27461 https://doi.org/10.1074/jbc.271.44.27456
  6. Luck AN and Mason AB (2012) Transferrin-mediated cellular iron delivery. Curr Top Membr 69, 3-35 https://doi.org/10.1016/B978-0-12-394390-3.00001-X
  7. Abdel Shakor AB, Atia MM, Kwiatkowska K and Sobota A (2012) Cell surface ceramide controls translocation of transferrin receptor to clathrin-coated pits. Cell Signal 24, 677-684 https://doi.org/10.1016/j.cellsig.2011.10.016
  8. Harding C, Heuser J and Stahl P (1983) Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol 97, 329-339 https://doi.org/10.1083/jcb.97.2.329
  9. Xu J, Zhou Z, Zeng L et al (2001) Cloning, expression and characterization of a novel human REPS1 gene. Biochim Biophys Acta 1522, 118-121 https://doi.org/10.1016/S0167-4781(01)00310-4
  10. Morinaka K, Koyama S, Nakashima S et al (1999) Epsin binds to the EH domain of POB1 and regulates receptormediated endocytosis. Oncogene 18, 5915-5922 https://doi.org/10.1038/sj.onc.1202974
  11. Oshiro T, Koyama S, Sugiyama S et al (2002) Interaction of POB1, a downstream molecule of small G protein Ral, with PAG2, a paxillin-binding protein, is involved in cell migration. J Biol Chem 277, 38618-38626 https://doi.org/10.1074/jbc.M203453200
  12. Oosterhoff JK, Penninkhof F, Brinkmann AO, Anton Grootegoed J and Blok LJ (2003) REPS2/POB1 is downregulated during human prostate cancer progression and inhibits growth factor signalling in prostate cancer cells. Oncogene 22, 2920-2925 https://doi.org/10.1038/sj.onc.1206397
  13. Tomassi L, Costantini A, Corallino S et al (2008) The central proline rich region of POB1/REPS2 plays a regulatory role in epidermal growth factor receptor endocytosis by binding to 14-3-3 and SH3 domain-containing proteins. BMC Biochem 9, 21 https://doi.org/10.1186/1471-2091-9-21
  14. Burke P, Schooler K and Wiley HS (2001) Regulation of epidermal growth factor receptor signaling by endocytosis and intracellular trafficking. Mol Biol Cell 12, 1897-1910 https://doi.org/10.1091/mbc.12.6.1897
  15. Kariya K, Koyama S, Nakashima S, Oshiro T, Morinaka K and Kikuchi A (2000) Regulation of complex formation of POB1/epsin/adaptor protein complex 2 by mitotic phosphorylation. J Biol Chem 275, 18399-18406 https://doi.org/10.1074/jbc.M000521200
  16. Ikeda M, Ishida O, Hinoi T, Kishida S and Kikuchi A (1998) Identification and characterization of a novel protein interacting with Ral-binding protein 1, a putative effector protein of Ral. J Biol Chem 273, 814-821 https://doi.org/10.1074/jbc.273.2.814
  17. Dergai O, Novokhatska O, Dergai M et al (2010) Intersectin 1 forms complexes with SGIP1 and Reps1 in clathrin-coated pits. Biochem Biophys Res Commun 402, 408-413 https://doi.org/10.1016/j.bbrc.2010.10.045
  18. Kannan N, Haste N, Taylor SS and Neuwald AF (2007) The hallmark of AGC kinase functional divergence is its C-terminal tail, a cis-acting regulatory module. Proc Natl Acad Sci U S A 104, 1272-1277 https://doi.org/10.1073/pnas.0610251104
  19. Moritz A, Li Y, Guo A et al (2010) Akt-RSK-S6 kinase signaling networks activated by oncogenic receptor tyrosine kinases. Sci Signal 3, ra64 https://doi.org/10.1126/scisignal.2000998
  20. Ikenoue T, Inoki K, Yang Q, Zhou X and Guan KL (2008) Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling. EMBO J 27, 1919-1931 https://doi.org/10.1038/emboj.2008.119
  21. Ahmed AR, Owens RJ, Stubbs CD et al (2019) Direct imaging of the recruitment and phosphorylation of S6K1 in the mTORC1 pathway in living cells. Sci Rep 9, 3408 https://doi.org/10.1038/s41598-019-39410-z
  22. Dalby KN, Morrice N, Caudwell FB, Avruch J and Cohen P (1998) Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk that are inducible by MAPK. J Biol Chem 273, 1496-1505 https://doi.org/10.1074/jbc.273.3.1496
  23. Yamaguchi A, Urano T, Goi T and Feig LA (1997) An Eps homology (EH) domain protein that binds to the Ral-GTPase target, RalBP1. J Biol Chem 272, 31230-31234 https://doi.org/10.1074/jbc.272.50.31230
  24. Dummler BA, Hauge C, Silber J et al (2005) Functional characterization of human RSK4, a new 90-kDa ribosomal S6 kinase, reveals constitutive activation in most cell types. J Biol Chem 280, 13304-13314 https://doi.org/10.1074/jbc.M408194200
  25. Oosterhoff JK, Kuhne LC, Grootegoed JA and Blok LJ (2005) EGF signalling in prostate cancer cell lines is inhibited by a high expression level of the endocytosis protein REPS2. Int J Cancer 113, 561-567 https://doi.org/10.1002/ijc.20612
  26. Nakashima S, Morinaka K, Koyama S et al (1999) Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors. EMBO J 18, 3629-3642 https://doi.org/10.1093/emboj/18.13.3629
  27. Drecourt A, Babdor J, Dussiot M et al (2018) Impaired transferrin receptor palmitoylation and recycling in neurodegeneration with brain iron accumulation. Am J Hum Genet 102, 266-277 https://doi.org/10.1016/j.ajhg.2018.01.003
  28. Penninkhof F, Grootegoed JA and Blok LJ (2004) Identification of REPS2 as a putative modulator of NF-kappaB activity in prostate cancer cells. Oncogene 23, 5607-5615 https://doi.org/10.1038/sj.onc.1207750
  29. van Dam EM and Stoorvogel W (2002) Dynamin-dependent transferrin receptor recycling by endosome-derived clathrin-coated vesicles. Mol Biol Cell 13, 169-182 https://doi.org/10.1091/mbc.01-07-0380
  30. Stoorvogel W, Oorschot V and Geuze HJ (1996) A novel class of clathrin-coated vesicles budding from endosomes. J Cell Biol 132, 21-33 https://doi.org/10.1083/jcb.132.1.21
  31. Futter CE, Gibson A, Allchin EH et al (1998) In polarized MDCK cells basolateral vesicles arise from clathrin-gammaadaptin-coated domains on endosomal tubules. J Cell Biol 141, 611-623 https://doi.org/10.1083/jcb.141.3.611
  32. Cho JH, Kim SA, Seo YS et al (2017) The p90 ribosomal S6 kinase-UBR5 pathway controls Toll-like receptor signaling via miRNA-induced translational inhibition of tumor necrosis factor receptor-associated factor 3. J Biol Chem 292, 11804-11814 https://doi.org/10.1074/jbc.M117.785170