Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mammalian prokineticins family comprises two conserved proteins, EG-VEGF/PROK1 and Bv8/PROK2, and their two highly related G protein-coupled receptors, PKR1 and PKR2. This signaling system has been linked to several important biological functions, including gastrointestinal tract motility, regulation of circadian rhythms, neurogenesis, angiogenesis and cancer progression, hematopoiesis, and nociception. Mutations in PKR2 or Bv8/PROK2 have been associated with Kallmann syndrome, a developmental disorder characterized by defective olfactory bulb neurogenesis, impaired development of gonadotropin-releasing hormone neurons, and infertility. Also, Bv8/PROK2 is strongly upregulated in neutrophils and other inflammatory cells in response to granulocyte-colony stimulating factor or other myeloid growth factors and functions as a pronociceptive mediator in inflamed tissues as well as a regulator of myeloid cell-dependent tumor angiogenesis. Bv8/PROK2 has been also implicated in neuropathic pain. Anti-Bv8/PROK2 antibodies or small molecule PKR inhibitors ameliorate pain arising from tissue injury and inhibit angiogenesis and inflammation associated with tumors or some autoimmune disorders.
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PMID:The Prokineticins: Neuromodulators and Mediators of Inflammation and Myeloid Cell-Dependent Angiogenesis. 2953 36

Prokineticins are two conserved small proteins (~8kDa), prokineticin 1 (PROK1; also called EG-VEGF) and prokineticin 2 (PROK2; also called Bv8), with an N-terminal AVITGA sequence and 10 cysteines forming 5 disulfide bridges. PROK1 and PROK2 bind to two highly related G protein-coupled receptors (GPCRs), prokineticin receptor 1 (PROKR1) and prokineticin receptor 2 (PROKR2). Prokineticins and their receptors are widely expressed. PROK1 is predominantly expressed in peripheral tissues, especially steroidogenic organs, whereas PROK2 is mainly expressed in the central nervous system and nonsteroidogenic cells of the testes. Prokineticins signaling has been implicated in several important physiological functions, including gastrointestinal smooth muscle contraction, circadian rhythm regulation, neurogenesis, angiogenesis, pain perception, mood regulation, and reproduction. Dysregulation of prokineticins signaling has been observed in a variety of diseases, such as cancer, ischemia, and neurodegeneration, in which prokineticins signaling seems to be a promising therapeutic target. Based on the phenotypes of knockout mice, PROKR2 and PROK2 have recently been identified as causative genes for idiopathic hypogonadotropic hypogonadism, a developmental disorder characterized by impaired development of gonadotropin-releasing hormone neurons and infertility. In vitro functional studies with these disease-associated PROKR2 mutations uncovered some novel features for this receptor, such as biased signaling, which may be used to understand GPCR signaling regulation in general.
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PMID:Prokineticins and their G protein-coupled receptors in health and disease. 3071 Oct 26