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Table 1 Interactions of each GRKs with intracellular proteins

From: Multiple functions of G protein-coupled receptor kinases

GRK isoform

Binding partner

Function

Reference

GRK2

Gαq

Regulation of Gαq signaling

[27, 28]

 

mGluR1

Regulation of G protein signaling in a phosphorylation-independent manner

[29]

 

Gβγ

Regulation of Gβγ-stimulated signaling

[31]

 

PDGFRβ

Phosphorylation of PDGFRβ by GRK2 reduces PDGFRβ signaling

[78, 79]

 

HDAC6

GRK2 associates with and phosphorylates HDAC6 to enhance α-tubulin deacetylase activity and cell motility

[81]

 

Akt

Interaction of GRK2 with Akt inhibits Akt activity

[82]

 

p38

Phosphorylation of p38 by GRK2 impairs MKK6-induced p38 activation

[88]

 

APC

Interaction of GRK2 with APC inhibits canonical Wnt signaling

[89]

 

GIT1

Interaction between GRK2 and GIT1 is important for GRK2-mediated cell motility

[90]

 

CDK2

Phosphorylation of GRK2 by CDK2 is important for cell cycle progression

[91]

 

MEK

GRK2 negatively regulates CC chemokine ligand 2-induced ERK activation by the interaction with MEK

[93]

 

IRS-1

Phosphorylation of IRS-1 by GRK2 mediates endothelin-1-induced insulin resistance

[94]

 

clathrin

Interaction of GRK2 with clathrin promotes GPCR internalization

[95]

 

PI3K

Translocation of PI3K to the plasma membrane is involved in GPCR internalization

[96]

 

HSP90

Interaction of GRK2 with HSP90 at the mitochondria promotes pro-death signaling after ischemic injury

[100]

GRK5

β-arrestin1

Phosphorylation of β-arrestin1 by GRK5 down-regulates G protein-independent signaling

[80]

 

HDAC5

Phosphorylation of HDAC5 promotes maladaptive cardiac hypertrophy

[83]

 

p105

Interaction with p105 results in inhibition of lipopolysaccharide-induced ERK activation

[84]

 

IκBα

Regulation of NF-κB signaling

[85, 86]

 

γ-tubulin centrin pericentrin

Co-localization of GRK5 with γ-tubulin, centrin, and pericentrin is important for regulation of microtubule nucleation and cell cycle progression

[92]

 

p53

Phosphorylation of p53 by GRK5 inhibits DNA damage-induced apoptosis

[106]

 

raptor

Grk5l, which is the closest homolog of GRK5 in zebrafish, interacts with raptor, and regulates mTOR signaling

[108]

GRK6

GIT1

GRK6 cooperates with GIT1 to enhance Rac1 activity, and promotes engulfment of apoptotic cells

[43]