Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, invades and replicates within susceptible hosts by disturbing host antimicrobial mechanisms. Although G protein-coupled receptors (GPCRs) are involved in most physiological and pathological activities of mammalian cells, the roles of GPCRs in Mtb invasion into host cell remain elusive. Here, we report that GPR160 expression is elevated at both mRNA and protein level in macrophages in response to BCG infection. Both the PiggyBac (PB) transposon-mediated mutation of gpr160 gene in mouse primary macrophages and siRNA-mediated knockdown of GPR160 in the human macrophage cell line THP-1 markedly reduced the entry of green fluorescent protein (GFP) expressing BCG (BCG-GFP), also operative in vivo. BCG infection-induced phosphorylation of ERK1/2 was significantly reduced in gpr160 mutated (gpr160(-/-)) macrophages relative to levels observed in wild type macrophages, while inhibition of ERK by specific inhibitor or knockdown ERK1/2 by specific siRNA markedly reduced entry of BCG. Finally, lower bacteria burdens and attenuated pathological impairments were observed in the lungs of BCG-infected gpr160(-/-) mice. Furthermore, gpr160(-/-) macrophages also exhibits reduced uptake of Escherichia coli and Francisella tularensis. Taken together, these findings suggest an important role of GPR160 in regulating the entry of BCG into macrophages by targeting the ERK signaling pathway. As GPCRs have proven to be successful drug targets in pharmaceutical industry, it's tempting to speculate that compounds targeting GPR160, a G protein-coupled receptor, could intervene in Mtb infection.
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PMID:G protein-coupled receptor160 regulates mycobacteria entry into macrophages by activating ERK. 2725 91

Treating neuropathic pain is challenging and novel non-opioid-based medicines are needed. Using unbiased receptomics, transcriptomic analyses, immunofluorescence, and in situ hybridization, we found that the expression of the orphan GPCR Gpr160 and GPR160 increased in the rodent dorsal horn of the spinal cord following traumatic nerve injury. Genetic and immunopharmacological approaches demonstrated that GPR160 inhibition in the spinal cord prevented and reversed neuropathic pain in male and female rodents without altering normal pain response. GPR160 inhibition in the spinal cord attenuated sensory processing in the thalamus, a key relay in the sensory discriminative pathways of pain. We also identified cocaine- and amphetamine-regulated transcript peptide (CARTp) as a GPR160 ligand. Inhibiting endogenous CARTp signaling in spinal cord attenuated neuropathic pain, whereas exogenous intrathecal CARTp evoked painful hypersensitivity through GPR160-dependent ERK and cAMP response element-binding protein (CREB). Our findings de-orphanize GPR160, identify it as a determinant of neuropathic pain and potential therapeutic target, and provide insights into its signaling pathways. CARTp is involved in many diseases including depression and reward and addiction; de-orphanization of GPR160 is a major step forward understanding the role of CARTp signaling in health and disease.
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PMID:GPR160 de-orphanization reveals critical roles in neuropathic pain in rodents. 3199 50