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Role of acidic amino acids in peptide substrates of the beta-adrenergic receptor kinase and rhodopsin kinase.

Publication ,  Journal Article
Onorato, JJ; Palczewski, K; Regan, JW; Caron, MG; Lefkowitz, RJ; Benovic, JL
Published in: Biochemistry
May 28, 1991

The beta-adrenergic receptor kinase (beta-ARK) phosphorylates G protein coupled receptors in an agonist-dependent manner. Since the exact sites of receptor phosphorylation by beta-ARK are poorly defined, the identification of substrate amino acids that are critical to phosphorylation by the kinase are also unknown. In this study, a peptide whose sequence is present in a portion of the third intracellular loop region of the human platelet alpha 2-adrenergic receptor is shown to serve as a substrate for beta-ARK. Removal of the negatively charged amino acids surrounding a cluster of serines in this alpha 2-peptide resulted in a complete loss of phosphorylation by the kinase. A family of peptides was synthesized to further study the role of acidic amino acids in peptide substrates of beta-ARK. By kinetic analyses of the phosphorylation reactions, beta-ARK exhibited a marked preference for negatively charged amino acids localized to the NH2-terminal side of a serine or threonine residue. While there were no significant differences between glutamic and aspartic acid residues, serine-containing peptides were 4-fold better substrates than threonine. Comparing a variety of kinases, only rhodopsin kinase and casein kinase II exhibited significant phosphorylation of the acidic peptides. Unlike beta-ARK, RK preferred acid residues localized to the carboxyl-terminal side of the serine. A feature common to beta-ARK and RK was a much greater Km for peptide substrates as compared to that for intact receptor substrates.

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Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

May 28, 1991

Volume

30

Issue

21

Start / End Page

5118 / 5125

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Substrate Specificity
  • Structure-Activity Relationship
  • Rhodopsin
  • Receptors, Adrenergic, beta
  • Protein Kinases
  • Phosphorylation
  • Peptides
  • Molecular Sequence Data
  • Glutamates
 

Citation

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Onorato, J. J., Palczewski, K., Regan, J. W., Caron, M. G., Lefkowitz, R. J., & Benovic, J. L. (1991). Role of acidic amino acids in peptide substrates of the beta-adrenergic receptor kinase and rhodopsin kinase. Biochemistry, 30(21), 5118–5125. https://doi.org/10.1021/bi00235a002
Onorato, J. J., K. Palczewski, J. W. Regan, M. G. Caron, R. J. Lefkowitz, and J. L. Benovic. “Role of acidic amino acids in peptide substrates of the beta-adrenergic receptor kinase and rhodopsin kinase.Biochemistry 30, no. 21 (May 28, 1991): 5118–25. https://doi.org/10.1021/bi00235a002.
Onorato JJ, Palczewski K, Regan JW, Caron MG, Lefkowitz RJ, Benovic JL. Role of acidic amino acids in peptide substrates of the beta-adrenergic receptor kinase and rhodopsin kinase. Biochemistry. 1991 May 28;30(21):5118–25.
Onorato, J. J., et al. “Role of acidic amino acids in peptide substrates of the beta-adrenergic receptor kinase and rhodopsin kinase.Biochemistry, vol. 30, no. 21, May 1991, pp. 5118–25. Pubmed, doi:10.1021/bi00235a002.
Onorato JJ, Palczewski K, Regan JW, Caron MG, Lefkowitz RJ, Benovic JL. Role of acidic amino acids in peptide substrates of the beta-adrenergic receptor kinase and rhodopsin kinase. Biochemistry. 1991 May 28;30(21):5118–5125.
Journal cover image

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

May 28, 1991

Volume

30

Issue

21

Start / End Page

5118 / 5125

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Substrate Specificity
  • Structure-Activity Relationship
  • Rhodopsin
  • Receptors, Adrenergic, beta
  • Protein Kinases
  • Phosphorylation
  • Peptides
  • Molecular Sequence Data
  • Glutamates