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Role of amino acid residues surrounding the phosphorylation site in peptide substrates of G protein-coupled receptor kinase 2 (GRK2)

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Abstract

A series of amino acid substitutions was made in a previously identified β-tubulin-derived GRK2 substrate peptide (404DEMEFTEAESNMN416) to examine the role of amino acid residues surrounding the phosphorylation site. Anionic amino acid residues surrounding the phosphorylation site played an important role in the affinity for GRK2. Compared to the original peptide, a modified peptide (Ac-EEMEFSEAEANMN-NH2) exhibited markedly higher affinity for GRK2, but very low affinity for GRK5, suggesting that it can be a sensitive and selective peptide for GRK2.

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Acknowledgments

The authors thank Ms. Sigemi Terakubo and Ms. Niño Okamura (St. Marianna University School of Medicine) for technical assistance. This work was supported by a Grant-in-Aid for Challenging Exploratory Research (KAKENHI Grant Number 15K12531) and for Scientific Research (C) (15K01319) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan.

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Authors and Affiliations

  1. Department of Microbiology, St. Marianna University School of Medicine, Sugao 2-16-1 Miyamae, Kawasaki, 216-8511, Japan

    Daisuke Asai & Hideki Nakashima

  2. Department of Advanced Medical Initiatives, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Masaharu Murata & Takahito Kawano

  3. Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorioka, Ikeda, Osaka, 563-8577, Japan

    Riki Toita

  4. Division of Biopharmaceutics and Pharmacokinetics, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishiro-dai, Suita, Osaka, 565-8565, Japan

    Jeong-Hun Kang

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  1. Daisuke Asai
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  2. Masaharu Murata
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  3. Riki Toita
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  4. Takahito Kawano
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  5. Hideki Nakashima
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  6. Jeong-Hun Kang
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Correspondence to Daisuke Asai or Jeong-Hun Kang.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Handling editor: T. Harkany.

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Asai, D., Murata, M., Toita, R. et al. Role of amino acid residues surrounding the phosphorylation site in peptide substrates of G protein-coupled receptor kinase 2 (GRK2). Amino Acids 48, 2875–2880 (2016). https://doi.org/10.1007/s00726-016-2345-6

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  • DOI: https://doi.org/10.1007/s00726-016-2345-6

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