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Targeting G protein-coupled receptor kinases to their receptor substrates

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Membrane association is essential for GRK function and because of this the GRKs have evolved complex regulatory mechanisms for associating with the membrane. Although the GRKs are highly homologous, each kinase utilizes a distinct mechanism for associating with the membrane, which makes it unique within the family. Initially, the carboxyl terminus of the GRKs was identified as the “membrane association domain” but recent evidence suggests that the amino terminus may also play a critical role in localizing the kinases to the membrane (Murga et al., 1996; Pitcher et al, 1996). It is within these two domains that the GRKs are most variable at the amino acid level. The GRKS exhibit an absolute requirement for phospholipids not only for association with the membrane but also for activity. There are differences in preference and binding sites for the phospholipids within the GRK family, which may reflect differential targeting of the GRKs to G protein-coupled receptors situated in different lipid environments. There are hundreds of G protein-coupled receptors and only six known GRKs. All the GRKs appear to phosphorylate the same receptor substrates in vitro (Sterne-Marr & Benovic, 1995; Premont et al., 1995). Receptor specificity, in a cellular

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Stoffel, R.H., Pitcher, J.A. & Lefkowitz, R.J. Targeting G protein-coupled receptor kinases to their receptor substrates. J. Membrane Biol. 157, 1–8 (1997). https://doi.org/10.1007/s002329900210

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Key words

  • G Protein-Coupled Receptor Kinase
  • βγ
  • Isoprenylation
  • Palmitoylation
  • PIP2