PMID: 9182987May 1, 1997Paper

Identification of a short sequence highly divergent between beta-adrenergic-receptor kinases 1 and 2 that determines the affinity of binding to betagamma subunits of heterotrimeric guanine-nucleotide-binding regulatory proteins

European Journal of Biochemistry
T T ChuangA De Blasi

Abstract

A 28-residue peptide (peptide G), derived from the C-terminal (W643-S670) of the beta-adrenergic receptor kinase (betaARK), was previously identified as the critical domain for binding to the betagamma subunits of the heterotrimeric guanine-nucleotide-binding regulatory protein (G betagamma). We observed that the 18-amino-acid core of this domain is poorly conserved between betaARK1 and betaARK2 and so may provide the basis for differences in G betagamma-binding properties. Specific antibodies raised against 18-residue peptides derived from the divergent sequences (peptides P1 and P2 for betaARK1 and betaARK2, respectively) competitively inhibited G betagamma-activation of the related betaARK subtype, confirming the involvement of this region in binding to G betagamma. Peptides P1 and P2 inhibited G betagamma-stimulated activity of both betaARK1 and betaARK2, with P2 being significantly more potent than P1 (IC50 of 179+/-5 microM for P2 and >500 microM for P1). The 28-residue peptides G showed the same relative inhibitory activities (IC50 = 48+/-5 microM for G2 and 146+/-8 microM for G1). This relative order of potency G2 > G1 approximately P2 > P1 was confirmed in a direct G betagamma-binding assay. No binding selectivity for ...Continue Reading

References

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Citations

Apr 20, 2004·Assay and Drug Development Technologies·Guido Iaccarino, Walter J Koch
Oct 6, 1998·Annual Review of Biochemistry·J A PitcherR J Lefkowitz
Mar 23, 2017·Journal of Cardiovascular Pharmacology·Sarah M Schumacher, Walter J Koch
Aug 16, 2003·Molecular Pharmacology·Susana SarnagoCristina Murga
Dec 18, 1998·The Journal of Biological Chemistry·P PenelaF Mayor
Sep 24, 1998·The American Journal of Physiology·G IaccarinoW J Koch
Feb 13, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·M S LombardiC J Heijnen

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