Meng, D., Lynch, M. J., Huston, E., Beyermann, M., Eichhorst, J., Adams, D. R., Klusmann, E., Houslay, M. D. and Baillie, G. S. (2009) MEK1 binds directly to βArrestin1, influencing both its phosphorylation by ERK and the timing of its isoprenaline-stimulated internalization. Journal of Biological Chemistry, 284(17), pp. 11425-11435. (doi: 10.1074/jbc.M806395200) (PMID:19153083) (PMCID:PMC2670148)
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Abstract
βArrestin is a multifunctional signal scaffold protein. Using SPOT immobilized peptide arrays, coupled with scanning alanine substitution and mutagenesis, we show that the MAPK kinase, MEK1, interacts directly with βarrestin1. Asp<sup>26</sup> and Asp<sup>29</sup> in the N-terminal domain of βarrestin1 are critical for its binding to MEK1, whereas Arg<sup>47</sup> and Arg<sup>49</sup> in the N-terminal domain of MEK1 are critical for its binding to βarrestin1. Wild-type FLAG-tagged βarrestin1 co-immunopurifies with MEK1 in HEKB2 cells, whereas the D26A/D29A mutant does not. ERK-dependent phosphorylation at Ser<sup>412</sup> was compromised in the D26A/D29A-βarrestin1 mutant. A cell-permeable, 25-mer N-stearoylated βarrestin1 peptide that encompassed the N-domain MEK1 binding site blocked βarrestin1/MEK1 association in HEK cells and recapitulated the altered phenotype seen with the D26A/D29A-βarrestin1 in compromising the ERK-dependent phosphorylation of βarrestin1. In addition, the MEK disruptor peptide promoted the ability of βarrestin1 to co-immunoprecipitate with endogenous c-Src and clathrin, facilitating the isoprenaline-stimulated internalization of the β2-adrenergic receptor.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Baillie, Professor George and Houslay, Professor Miles and Huston, Dr Elaine |
| Authors: | Meng, D., Lynch, M. J., Huston, E., Beyermann, M., Eichhorst, J., Adams, D. R., Klusmann, E., Houslay, M. D., and Baillie, G. S. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience College of Medical Veterinary and Life Sciences > School of Life Sciences |
| Journal Name: | Journal of Biological Chemistry |
| Journal Abbr.: | J Biol Chem. |
| Publisher: | American Society for Biochemistry and Molecular Biology, Inc. |
| ISSN: | 0021-9258 |
| ISSN (Online): | 1083-351X |
| Published Online: | 19 January 2009 |
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