INT85684

Context Info Confidence 0.79 First Reported 1999 Last Reported 2009 Negated 0 Speculated 0 Reported most in Body Documents 7 Total Number 7 Disease Relevance 0.70 Pain Relevance 2.39

signal transduction (Gpbar1) plasma membrane (Gpbar1) signal transducer activity (Gpbar1)

Anatomy Link Frequency pits 1 Gpbar1 (Mus musculus)

Pain Link Frequency Relevance Heat Kinase C 9 100.00 agonist 92 99.60 Inflammatory response 1 98.24 tolerance 23 96.28 mu opioid receptor 19 95.80 chemokine 1 92.48 opioid receptor 26 90.48 Pain 16 90.00 Morphine 12 89.28 addiction 9 83.24

Disease Link Frequency Relevance Heat INFLAMMATION 3 97.88 Pain 17 90.00 Hypothermia 2 84.40 Acquired Immune Deficiency Syndrome Or Hiv Infection 75 83.40 Tremor 1 68.48 Targeted Disruption 10 43.76 Glioma 13 5.00 Infection 10 5.00 Inflammatory Pain 8 5.00 Hyperalgesia 5 5.00

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Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

From current studies, it is known that various phosphorylation steps, such as protein kinase C (PKC) and G protein-coupled receptor (GPCR) kinase (GRK) regulate endocytosis.

Phosphorylation (phosphorylation) of GPCR associated with kinase c

1) Confidence 0.79 Published 2004 Journal Ann. N. Y. Acad. Sci. Section Abstract Doc Link 15542739 Disease Relevance 0 Pain Relevance 0.93

The efficiency of GPCR signaling is tightly regulated and ultimately limited by the coordinated phosphorylation of the receptors by specific GPCR kinases and the subsequent interaction of the phosphorylated receptors with beta-arrestin 1 and beta-arrestin 2.

Phosphorylation (phosphorylation) of GPCR

2) Confidence 0.71 Published 1999 Journal Science Section Abstract Doc Link 10617462 Disease Relevance 0.09 Pain Relevance 0.65

G protein-coupled receptor kinase 5 (GRK5) is a member of a family of enzymes that phosphorylate activated G protein-coupled receptors (GPCR).

Phosphorylation (phosphorylate) of GPCR

3) Confidence 0.66 Published 1999 Journal Neuron Section Abstract Doc Link 10624964 Disease Relevance 0.22 Pain Relevance 0.07

Classically, agonist binding results in phosphorylation of the GPCR, which in turn leads to recruitment of ?

Phosphorylation (phosphorylation) of GPCR associated with agonist

4) Confidence 0.33 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2672171 Disease Relevance 0 Pain Relevance 0.19

However, the Src inhibitor, PP1 or the expression of a dominant-negative Src mutant, will reduce GPCR-mediated transphosphorylation of the EGFR and GPCR-mediated ERK activation to varying degrees (partial to total), suggesting that at least two different tyrosine kinases can be involved [18].

Phosphorylation (transphosphorylation) of GPCR

5) Confidence 0.25 Published 2002 Journal BMC Pharmacol Section Body Doc Link PMC88976 Disease Relevance 0 Pain Relevance 0.11

Reports of GPCR endocytosis in the absence of GRK phosphorylation [24-26] suggest that the removal of C-terminal phosphorylation sites may reduce the affinity of the receptor for proteins that mediate endocytosis without preventing the protein-protein interactions that are essential for internalization.

Phosphorylation (phosphorylation) of GPCR

6) Confidence 0.17 Published 2005 Journal BMC Biol Section Body Doc Link PMC551613 Disease Relevance 0 Pain Relevance 0.35

Upon SDF-1 binding, CXCR4 is rapidly phosphorylated by GPCR kinase (GRK) and internalized via clathrin-coated pits [19].

Phosphorylation (phosphorylated) of GPCR kinase in pits

7) Confidence 0.09 Published 2008 Journal Virol J Section Body Doc Link PMC2262066 Disease Relevance 0.39 Pain Relevance 0.10

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