Gene/Protein
Disease
Symptom
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Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
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Target Concepts:
Gene/Protein
Disease
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Query: EC:2.7.11.12 (
PKG
)
2,515
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The cGMP/
cGMP-dependent protein kinase
I (cGKI) signaling pathway plays an important role in spinal nociceptive processing. However, downstream targets of cGKI in this context have not been identified to date. Using a yeast two-hybrid screen, we isolated
cysteine-rich protein 2
(
CRP2
) as a novel cGKI interactor in the spinal cord.
CRP2
is expressed in laminas I and II of the mouse spinal cord and is colocalized with cGKI, calcitonin gene-related peptide, and isolectin B4. Moreover, the majority of
CRP2
mRNA-positive dorsal root ganglion (DRG) neurons express cGKI and peripherin.
CRP2
is phosphorylated in a cGMP-dependent manner, and its expression increases in the spinal cord and in DRGs after noxious stimulation of a hindpaw. To elucidate the functional role of
CRP2
in nociception, we analyzed mice with a targeted deletion of
CRP2
.
CRP2
-deficient (
CRP2
-/-) mice demonstrate normal behavioral responses to acute nociception and after axonal injury of the sciatic nerve, but increased nociceptive behavior in models of inflammatory hyperalgesia compared with wild-type mice. Intrathecal administration of cGMP analogs increases the nociceptive behavior in wild-type but not in
CRP2
-/- mice, indicating that the presence of
CRP2
is important for cGMP-mediated nociception. These data suggest that
CRP2
is a new downstream effector of cGKI-mediated spinal nociceptive processing and point to an inhibitory role of
CRP2
in the generation of inflammatory pain.
...
PMID:Cysteine-rich protein 2, a novel downstream effector of cGMP/cGMP-dependent protein kinase I-mediated persistent inflammatory pain. 1825 52
