Prokineticins are a pair of signal factors involved in many physiological processes by binding to two closely related G-protein-coupled receptors, PKR1 and PKR2. Recently, mutations in prokineticin 2 (PK2) and PKR2 are found to be associated with Kallmann syndrome and/or idiopathic hypogonadotropic hypogonadism, disorders characterized by delayed puberty and infertility. However, little is known how PKRs interact and activate G-proteins to elicit signal transduction. In the present study, we took advantage of one disease-associated mutation (R164Q) located in the second intracellular (IL2) loop of PKR2, to investigate the role of IL2 loop in the cell signaling, G-protein binding and receptor trafficking. R164Q mutant PKR2 showed normal cell surface expression and ligand binding capacity. However, the PKR2 signaling was abolished by R164Q mutation. We demonstrated that R164Q mutation disrupted the interaction of IL2 loop to the G␣ q , G␣ i , and G␣ 16 -proteins. A positive-charged amino acid at this position is required for proper function, and the signaling efficacy and potency depend on the net amount of positive charges. We also demonstrated that the interactive partner of Arg-164 may localize in the C-terminal five residues of G␣ q -protein. A series of mutation analysis indicated that the basic amino acids at the C terminus of IL2 loop may function cooperatively in GPCRs. Furthermore, R164Q mutation also results in minimal ligand-induced endocytosis of PKR2. As many GPCRs share structural homology in the C terminus of IL2 loop, our findings may have general application in understanding structure and function of GPCRs. G-protein-coupled receptors (GPCRs)2 are the largest family of membrane-spanning proteins that transduce numerous extracellular signals including light, odorants, hormones, neurotransmitters, and chemokines to the interior of cells and play fundamental roles in regulation of cellular functions. The structure of GPCRs consists of seven transmembrane (TM) helices, with three intracellular loops (IL1-3) and the cytoplasmic C-terminal tail. The extracellular ligands activate GPCRs and enable the receptors to interact with and activate distinct sets of heterotrimeric G proteins (e.g. G␣␤␥) (1).Prokineticins are a pair of signal factors involved in a variety of physiological processes, including gastrointestinal mobility, circadian rhythms, emotion, nociception, angiogenesis, and neurogenesis (2-5). Prokinticins execute their functions by binding to two closely related GPCRs, PKR1 and PKR2 (6, 7). It has been shown that activation of prokineticin receptors (PKRs) leads to accumulation of inositol phosphate and mobilization of intracellular Ca 2ϩ via G␣ q/11 proteins (6). In addition, PKRs may inhibit cAMP accumulation, presumably through G␣ i/o proteins (8). Furthermore, PKRs have been shown to stimulate mitogen-activated protein kinase via G␣ o protein-mediated signaling (6). However, little is known about the structure-function relationships in PKRs, and more extensive research is necessary to iden...

Background Ring chromosomes can be formed by terminal breaks of two arms of a chromosome and their rejoining, leading to a loss of genetic material. They may also be formed by telomere-telomere fusions with no deletion, resulting in the formation of a complete ring. Mosaic X-ring chromosomes are extremely rare and have highly variable phenotypes. Here, we report a case with a mosaic X-ring chromosome in a patient with Turner syndrome, and we illustrate the unreported complicated mechanism using chromosome analysis and fluorescence in situ hybridization (FISH). Case presentation A 10-year-old girl of short stature presenting Turner syndrome was admitted to our hospital. The patient’s clinical characteristics were subsequently documented. Genetic analysis showed a karyotype of mostly 45,X[140]/46,X,r(X)[60]. The X ring chromosome was cytogenetically characterized as 45,X/46,X,r(X)(p22.32q21.1), with a length of approximately 74 Mb. Conclusions Taken together, we report a rare case with a mosaic X ring chromosome in Turner syndrome and we believe this case expands our collective knowledge of mosaic structural chromosomal disorders and provides new insight into clinical management and genetic counseling for Turner syndrome.

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