Grk6 (rat) - manual literature research

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manually from cached publications (publications/PMID_*.md) and PubMed searches.

Identity

• Rat G protein-coupled receptor kinase 6, UniProtKB P97711 (Swiss-Prot; RGD:61986; GeneID 59076).
  An unreviewed TrEMBL entry for the same gene (A0ABK0L927, 589 aa, Ensembl ENSRNOP00000101572)
  also exists; GOA annotations are keyed to P97711.
• 576 aa; RGS-homology domain (53-171), protein kinase domain (186-448) and AGC-kinase C-terminal
  domain (449-514) [file:rat/Grk6/Grk6-uniprot.txt]. Member of the GRK4/5/6 subfamily of GRKs.
• Cloned from rat brain: "a protein of 576 amino acids that is 96.7% identical and 97.9% similar
  to its human counterpart. mRNA was detectable in all brain areas examined." PMID:9387888

Activity

• GRKs phosphorylate agonist-occupied GPCRs, which promotes arrestin binding and desensitization.
  UniProt (by similarity to human P43250): "Specifically phosphorylates the activated forms of G
  protein-coupled receptors." [file:rat/Grk6/Grk6-uniprot.txt]
• GRK6 is palmitoylated on a C-terminal Cys cluster (Cys561/562/565): "Palmitoylation of GRK6
  appears essential for membrane association, since palmitoylated kinase was found only in the
  membrane fraction." PMID:7961702
• "Palmitoylated GRK6 is 10-fold more active at phosphorylating beta2-adrenergic receptor than
  nonpalmitoylated wild-type GRK6 or a nonpalmitoylatable mutant GRK6." and "Palmitoylated GRK6 is
  associated with the membrane, while nonpalmitoylated GRK6 remains cytosolic." PMID:9819198

Rat functional studies

• Myometrium (primary uterine smooth muscle cells): "Expression of (K215R)GRK6 increased by
  approximately 70% the cAMP response to isoproterenol without effect on forskolin stimulation"
  and "These results strongly suggest that endogenous GRK6 mediate homologous beta-AR
  desensitization in myometrial cells." [PMID:12810562; abstract only]
• Hippocampal neurons, M1 muscarinic receptor: "Inhibition of endogenous GRK6 ... by the
  introduction of catalytically inactive (K215R)GRK6, partially reversed the attenuation of
  agonist-induced responsiveness, whereas overexpression of wild-type GRK6 increased receptor
  desensitization." PMID:15115810
• In mature synaptically active neurons, "expression of K215RGRK6 did not affect M1 mACh receptor
  desensitization in TTx-treated, or spontaneously synaptically-active neurons (Fig. 3e). However,
  inhibition of endogenous GRK6 appeared to partially prevent picrotoxin-enhanced M1 mACh receptor
  desensitization (Fig. 3e)." [PMID:17908240; full text read]. The dominant role in these mature
  neurons is GRK2 (kinase-dependent) plus PKC.
• Spinal cord injury: GRK6 protein rises in microglia after injury and after LPS in vitro
  ("up-regulation in GRK6 protein expression after LPS stimulation was time- and
  dose-dependent") PMID:23359120 - expression only.

Mouse knockout data (donor for ISO rows)

• "The present study indicates that postsynaptic D2-like dopamine receptors are physiological
  targets for GRK6" PMID:12718862.
• GRK6-deficient T cells "were strikingly impaired in their ability to respond to CXCL12" while
  CXCL12-stimulated membrane GTPase activity increased PMID:12032308 - GRK6 both desensitizes
  CXCR4 and is required for chemotaxis.

Interactions

• Rat GRK6 interacts with GIT1 (UniProt SUBUNIT, ECO:0000269 PubMed:9826657).