Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
To learn more about potential downstream effectors involved in these melanocortinergic obesity syndromes , we have examined expression of the orexigenic peptides galanin and neuropeptide Y ( NPY ) , as well as the anorexigenic POMC in lethal yellow ( A ( y ) ) , MC 4 R knockout ( MC 4 RKO ) , and leptin deficient ( ob / ob ) mice . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Recent studies in animal models elucidated a central role of alpha MSH in the regulation of food intake by activation of the brain melanocortin 4 receptor ( MC 4 R ; refs 3 5 ) and the linkage of human obesity to chromosome 2 in close proximity to the POMC locus , led to the proposal of an association of POMC with human obesity . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
AGRP containing neurons are not visualized in a number of areas , including portions of the amygdala , thalamus , and brain stem , that express MC 3 R and MC 4 R messenger RNA and receive innervation from POMC neurons that serve as the source of melanocortin agonists . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
POMC is the precursor of alpha melanocyte stimulating hormone ( alpha MSH ) , which binds to the melanocortin receptor MC 4 R in the brain , decreases appetite , and activates lipid metabolism . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Agouti related protein ( AGRP ) is a recently discovered orexigenic neuropeptide that inhibits the binding and action of alpha melanocyte stimulating hormone derived from proopiomelanocortin ( POMC ) at the melanocortin 3 receptor ( MC3R ) and melanocortin 4 receptor ( MC4R ) and has been proposed to function primarily as an endogenous melanocortin antagonist . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
In humans , mutations in leptin , leptin receptor , prohormone convertase 1 ( PC 1 ) , pro opiomelanocortin ( POMC ) , melanocortin 4 receptor ( MC 4 R ) , and peroxisome proliferator activated receptor ( PPAR ) gamma 2 genes have been described in patients with severe obesity . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
The melanocortin 4 receptor ( MC4R ) is a seven , transmembrane G protein coupled receptor whose ligand , alpha melanocyte stimulating hormone ( alpha MSH ) , is a post translational derivative of pro opiomelanocortin ( POMC ) . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Expression of the Pomc gene in the central nervous system results in the production of melanocortin peptides , which bind to the melanocortin 4 receptor ( MC 4 R ) and inhibit food intake . ^^^ Recently , Pomc knockout mice were generated and shown to develop hyperphagia and obesity with a time course and severity comparable to MC 4 R knockout mice , whereas daily administration of a stable alpha melanocyte stimulating hormone analogue reversed this effect . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Regulation of appetite by melanocortin and its receptors ] . alpha , beta , gamma MSH and ACTH are derived from the same precursor , POMC ( proopiomelanocortin ) , and are classified as melanocortin . alpha MSH plays an important role in the regulation of appetite and energy expenditure via central melanocortin receptor , melanocortin 4 receptor ( MC4R ) , which is expressed mainly in hypothalamus . alpha MSH or its analogue shows inhibitory effect on appetite and inversely MC4R antagonist stimulates appetite . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
The genetic basis of childhood obesity has been elucidated to some extent through the discovery of leptin , the ob gene product , and the increasing knowledge on the role of neuropeptides such as POMC , neuropeptide Y ( NPY ) and the melanocyte concentrating hormone receptors ( MC4R ) . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
The MC 4 R is activated by alpha melanocyte stimulating hormone [ alpha MSH ; a cleavage product of pro opiomelanocortin ( POMC ) , which is expressed in the other ARC neurones ] and inhibits feeding . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
We also investigated potential downstream targets of leptin responsive NPY and POMC neurons by assessing the distribution of the melanocortin 4 receptor ( MC 4 R ) mRNA and Y 1 and Y 5 NPY receptor mRNA in chemically defined neurons . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Leptin directly exerts its anorexigenic effects on hypothalamic arcuate nucleus . alpha melanocyte stimulating hormone ( alpha MSH ) derived from proopiomelanocortin ( POMC ) and melanocortin 4 receptor ( MC 4 R ) have been reported to be involved in the downstream of leptin actions . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Bioactive peptides derived from the prohormone , pro opiomelanocortin ( POMC ) , are generated in neurons of the hypothalamus and act as endogenous ligands for the melanocortin 4 receptor ( MC4R ) , a key molecule underlying appetite control and energy homeostasis . ^^^ We predict that further research into hypothalamic POMC processing , and the proteolytic enzymes involved , may yield important new clues on how flux through the MC4R pathway is regulated . . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
In humans , mutations in leptin , leptin receptor , proopiomelanocortin ( POMC ) , melanocortin 4 receptor ( MC4R ) and prohormone convertase 1 ( PC 1 ) have been described in patients with severe obesity . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Finally , an awareness of possible genetic causes of eating disorders will help determine the causes and thus the treatments in children and adolescents with eating disorders , as exemplified by obese patients with mutations in the POMC , PC 1 , leptin , and MC4R loci . . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
The genetic basis of childhood obesity has been elucidated to some extent through the discovery of leptin , the ob gene product , and the increasing knowledge on the role of neuropeptides such as POMC , neuropeptide Y ( NPY ) and the melanocyte concentrating hormone receptors ( for example , MC4R ) . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Pro opiomelanocortin ( POMC ) , MC3R , and MC4R knockouts are obese and are now being used to further analyze melanocortin receptor function . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Exceptional mutations of the leptin gene and its receptor , pro opiomelanocortine ( POMC ) , prohormone convertase 1 ( PC 1 ) and more frequently , mutations in the melanocortin receptor 4 ( 1 to 4 % of very obese cases ) have been described . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Taking into account fat content by ANCOVA reveals , however , increases in both NPY mRNA and POMC mRNA due to melanocortin 4 receptor ( MC4R ) deficiency . ^^^ We conclude that hyperphagia , not hypometabolism , is the primary disturbance initiating excessive fat deposition in MC4R deficient mice at weaning and that the overall changes in NPY and POMC expression tend to antagonize the onset of excessive fat deposition . . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
We examined hypothalamic gene expressions of Ob Rb , NPY , AgRP , POMC , MC 4 R , and preproorexins in pregnant Wistar rats at day 19 of gestation . ^^^ No differences were found in mRNA expression of Ob Rb , POMC , MC 4 R , NPY or preproorexin between virgin and pregnant animals . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Two melanocortin receptors ( MC3R , MC4R ) are expressed in brain regions receiving projections of POMC fibers , most of which also receive projections from a population of ARC neurons that co express neuropeptide Y ( NPY ) and the MC3R / MC4R antagonist agouti related peptide ( AgRP ) . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
OBJECTIVE : Mutations in the pro opiomelanocortin and melanocortin 4 receptor genes ( POMC and MC4R ) cause monogenic obesity , and the POMC locus ( 2p21 ) has been linked to leptin levels and body mass index ( BMI ) . ^^^ We searched for monogenic obesity due to mutations in POMC and MC4R among morbidly obese Swedes and studied the association of POMC variants with BMI and serum leptin levels . ^^^ DESIGN : MC4R and POMC were screened for mutations in 102 obese Swedish subjects ( 40+ / 11 y , 41 . 3+ / 5 . 0 kg / m ( 2 ) ) using the single strand conformation polymorphism technique . ^^^ RESULTS : No cases of monogenic obesity due to mutations in POMC or MC4R were identified and none of the four common POMC polymorphisms ( RsaI , ins 56 , Glu188Gly and C8246T ) were associated with obesity . ^^^ CONCLUSIONS : Monogenic forms of obesity due to mutations in POMC and MC4R are rare in Swedish obese patients . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Genetic , biochemical and pharmacological studies in humans and rodents have established that signalling through the G protein coupled melanocortin 4 receptor ( MC4R ) by pro opiomelanocortin ( POMC ) derived ligands plays a critical role in the central suppression of appetite . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
In young ( 35 to 56 day old ) and middle aged ( 9 mo old ) wild type ( + / + ) and melanocortin 4 receptor ( MC4R ) deficient ( + / , / ) mice , expressions of neuropeptide Y ( NPY ) , agouti related protein ( AGRP ) , pro opiomelanocortin ( POMC ) , and cocaine and amphetamine regulated transcript ( CART ) were analyzed in the arcuate nucleus ( ARC ) and adjacent regions comprising the dorsomedial ( DMN ) and ventromedial ( VMN ) nucleus . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Altered levels of POMC , AgRP and MC 4 R mRNA expression in the hypothalamus and other parts of the limbic system of mice prone or resistant to chronic high energy diet induced obesity . ^^^ This study has investigated the levels of mRNA expression of proopiomelanocortin ( POMC ) , agouti related protein ( AgRP ) and the melanocortin 4 receptor ( MC 4 R ) in diet induced obese ( DIO ) and diet resistant ( DR ) mice . ^^^ In conclusion , this study has demonstrated that differential expression of POMC , AgRP and MC 4 R mRNA levels exists in DIO , DR and LF mice . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
The study shows that some parts of the MC system are highly conserved through vertebrate evolution , such as regions in POMC coding for ACTH , alpha MSH , and beta MSH , the C terminal region of AGRP , key binding units within the MC1R , MC2R , MC4R , and MC5R , synteny blocks around the MCRs , pharmacological properties of the MC2R , whereas other parts in the system are either missing , such as the MC3R and gamma MSH , or different as compared to mammals , such as the affinity of ACTH and MSH peptides to MC1R and MC4R and the anatomical expression pattern of the MCRs . . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Interactions between pro opiomelanocortin ( POMC ) derived peptides , agouti related protein ( AGRP ) and the melanocortin 4 receptor ( MC 4 R ) are central to energy homeostasis . ^^^ There was no significant difference in the potency of inhibition by AGRP ( 83 132 ) or agouti ( 87 132 ) at the MC 4 R , regardless of which POMC peptide was used as an agonist . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Mice that are engineered to be deficient for the melanocortin 4 receptor ( MC4R ) or pro opiomelanocortin ( POMC ) and those that overexpress agouti or agouti related protein ( AgRP ) all have a characteristic obese phenotype typified by hyperphagia , increased linear growth , and metabolic defects . ^^^ The central melanocortin system modulates energy homeostasis through the actions of the agonist , alpha melanocyte stimulating hormone ( alpha MSH ) , a POMC cleavage product , and the endogenous antagonist AgRP on the MC3R and MC4R . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Food intake , energy expenditure , adiposity , BAT UCP 1 , and leptin expression in white fat as well as hypothalamic expressions of MC3R , MC4R , POMC , AgRP and NPY were assessed . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
METHODS : We genotyped polymorphisms in the melanocortin 4 receptor ( MC4R ) , melanocortin 3 receptor ( MC3R ) , neuropeptide Y ( NPY ) , neuropeptide Y Y 1 receptor ( NPY Y1R ) , cocaine and amphetamine regulated transcript ( CART ) , agouti related protein ( AGRP ) , and pro opiomelanocortin ( POMC ) genes in 669 subjects ( age ( X+ / s . d . ) : parents : 52+ / 3 . 4 y ; offspring : 28+ / 8 . 7 y ) . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Male rats were subjected to rapid eye movement sleep deprivation stress and the levels of proopiomelanocortin ( POMC ) , MC3R , MC4R and MC5R transcripts in the hypothalamic pituitary adrenal axis ( HPA ) determined by real time PCR . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Administration of JKC 363 , a selective MC4R specific antagonist , coupled with [ Gln ( 6 ) ] alpha MSH ND , specifically reversed the [ Gln ( 6 ) ] alpha MSH ND induced inhibition of food intake , but also reversed the hypothalamic expression levels of neuropeptides such as AGRP , NPY , MCH , and POMC , which suggests [ Gln ( 6 ) ] alpha MSH ND can function as a selective MC4R agonist . . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
These SNPs , as well as SNPs in pro opiomelancortin ( POMC ) , leptin ( LEP ) and melanocortin 4 receptor ( MC4R ) , were evaluated for associations with average daily gain , end of test rib eye area , shipping weight and hot carcass weight in a group of 256 steers using a general linear model . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
The knock out of POMC gene or MC 4 R gene causes obesity in animals . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Melanocortin 4 receptor gene ( MC4R ) variants are associated with obesity and binge eating disorder ( BED ) , whereas the more prevalent proopiomelanocortin ( POMC ) and leptin receptor gene ( LEPR ) mutations are rarely associated with obesity or BED . ^^^ The complete coding regions of MC4R , POMC , and leptin binding domain of LEPR were comparatively sequenced in 300 patients ( 233 women and 67 men ; mean + / SEM age , 42 + / 1 years ; mean + / SEM body mass index , 43 . 5 + / 0 . 3 kg / m2 ) undergoing laparoscopic gastric banding . ^^^ Nineteen patients ( 6 . 3 % ) carried 8 MC4R variants , 144 ( 48 . 0 % ) carried 13 POMC variants , and 247 ( 82 . 3 % ) carried 11 LEPR variants . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Regulation of CRF , POMC and MC4R gene expression after electrical foot shock stress in the rat amygdala and hypothalamus . ^^^ We investigated the effects of electrical foot shock stress on the melanocortin signaling cascade and the hypothalamus pituitary adrenal ( HPA ) system by observing levels of mRNA expression of corticotropin releasing factor ( CRF ) , pro opiomelanocortin ( POMC ) , and melanocortin receptor subtype 4 ( MC4R ) in the rat amygdala and hypothalamus . ^^^ In the amygdala , the expression of MC4R and POMC mRNA as well as CRF mRNA was significantly increased by electrical foot shock stress . ^^^ In the hypothalamus , MC4R and POMC mRNA increased , but CRF mRNA remained unchanged . ^^^ The duration of increased gene expression of MC4R and POMC in the amygdala was more sustained than in the hypothalamus . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Here we report variants of the proopiomelanocortin ( POMC ) and melanocortin receptor 4 ( MC4R ) genes detected in severely obese adults living in southern Italy . ^^^ POMC and MC4R were genotyped by sequencing analysis . ^^^ RESULTS : Of the obese participants , 1 . 5 % had mutations in POMC exon 3 ( new mutations , P231L and E244X ; known , R236G ) and 2 . 5 % had MC4R mutations ( new mutations , W174C , Q43X , S19fsX51 , and I317V ; known , A175T ) . ^^^ Gene polymorphisms were identified in similar percentages of severely obese and nonobese individuals , i . e . , respectively , 52 . 5 % and 51 % ( POMC ) and 1 % and 2 % ( MC4R ) . ^^^ CONCLUSIONS : We detected 2 new POMC mutations and 4 new MC4R mutations in a large number of severely obese adults living in southern Italy . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
The pro opiomelanocortin ( POMC ) melanocortin 4 receptor ( MC 4 R ) is also important for leptin signaling . ^^^ From studies of agouti yellow ( A ( y ) / a ) obese mice , a model of a defect in POMC MC 4 R signaling , we concluded that the histamine H ( 1 ) R signaling pathway is independent of the POMC MC 4 R complex in regulating food intake , energy metabolism , and adiposity . . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Several genes from these pathways have been tested include genes involved in steroid hormone biosynthesis and metabolism ( StAR , CYP 11 , CYP 17 , CYP 19 HSD17B1 3 , HSD3B1 2 ) , gonadotropin and gonadal hormones action ( ACTR 1 , ACTR2A B , FS , INHA , INHBA B , INHC , SHBG , LHCGR , FSHR , MADH 4 , AR ) , obesity and energy regulation ( MC4R , OB , OBR , POMC , UCP 2 3 ) , insulin secretion and action ( IGF 1 , IGF1R , IGFBPI 1 3 , INS VNTR , IR , INSL , IRS 1 2 , PPARG ) and many others . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Loss of function mutations of genes encoding POMC , or of either of two melanocortin receptors expressed in the central nervous system ( MC3R , MC4R ) , are associated with obesity . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Yet , the highest MC 4 R density in the brain is found in the dorsal motor nucleus of the vagus nerve , situated subjacent to the commissural nucleus of the solitary tract , a site of pro opiomelanocortin mRNA expression . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Rare mutations of the leptin gene and its receptor , proopiomelanocortin , or more frequently , melanocortin receptor 4 mutations , are evidence of the existence of an obesity gene . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Activation of MC 4 R by agonists such as alpha melanocyte stimulating hormone ( a cleavage product of pro opiomelanocortin which is expressed in ARC neurones ) inhibits feeding and causes weight loss . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Contrary to the obese phenotypes shown in MC4R , proopiomelanocortin , or leptin deficient mice , our results showed that CART deficiency predisposed mice to become obese on a calorically dense diet . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
In situ hybridization failed to detect altered CNS expression levels for proopiomelanocortin , Mc3r , Mc4r , or NPY mRNAs in Agrp ( / ) mice . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
The cloning of the melanocyte stimulating hormone ( MSH ) and adrenocorticotropic hormone ( ACTH ) receptors ( MC 1 R and MC 2 R , respectively ) recently has led to the identification of three additional melanocortin receptors , MC 3 R , MC 4 R , and MC 5 R . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
The melanocortin receptor family includes the melanocyte stimulating hormone receptor ( MSH R ) , adrenocorticotropic hormone receptor ( ACTH R ) , and two neural receptors , MC 3 R and MC 4 R . ^^^ In the human these receptors map to 16q24 ( MSH R ) , 18p11 . 2 ( ACTH R ) , 20q13 . 2 ( MC 3 R ) , and 18q22 ( MC 4 R ) . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
In the four types of currently cloned ACTH receptors ( melanocortin receptors ) , two of them ( MC3R and MC4R ) are prevalent in the CNS . . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
In addition , the MC 4 R antagonist [ D Arg 8 ] ACTH ( 4 10 ) , inhibited the alpha MSH effect , indicating that the MC 4 R mediated stimulation of neurite outgrowth by alpha MSH . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
In contrast , the other MCR subtypes ( MC 1 R , MC 3 R , MC 4 R , MC 5 R ) recognize a common group of ligands that includes various forms of MSH as well as ACTH ; nevertheless they do exhibit important differences in ligand selectivity . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Our data confirmed that Agrp is not an antagonist of ACTH at the level of MC 2 R and that its sustained effect on ACTH induced steroidogenesis did not involve its antagonistic properties at the level of MC 4 R . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
We conclude that the hypotension and bradycardia elicited by the release of alpha MSH from arcuate neurons is mediated by neural melanocortin receptors ( MC 4 R / MC3 R ) located in the DVC , whereas the similar effects of beta endorphin , a peptide derived from the same precursor , are mediated by opiate receptors at the same site . ^^^ In contrast , neither MC 3 R nor MC 4 R is involved in the centrally mediated pressor and tachycardic actions of gamma MSH , which , likely , are mediated by an as yet unidentified receptor . . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Recently , it has also been reported that melanocyte stimulating hormone ( MSH ) and melanocortin 4 receptor ( MC4R ) are the key components of the hypothalamic response to obesity . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
In contrast , mouse agouti protein antagonized desacetyl alpha MSH much more effectively and potently than alpha MSH coupling the MC 4 R to the PKA signaling pathway . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
We have examined the effects of underfeeding and obesity on the density of hypothalamic melanocortin MC 3 and MC 4 receptors ( MC 3 R and MC 4 R , respectively ) , which may mediate the hypophagic effects of alpha melanocyte stimulating hormone ( MSH ) in the rat . ^^^ MC 3 R and MC 4 R were measured by quantitative autoradiography in brain sections using 125I labeled Nle 4 D Phe 7 alpha MSH ( 125I NDP MSH ) and discriminated by masking MC 3 R with excess unlabelled gamma 2 MSH . ^^^ We suggest that increased density of MC 4 R with food restriction and in obese Zucker rats reflects receptor upregulation secondary to decreased release of alpha MSH , consistent with increased hunger in these models . ^^^ Conversely , downregulation of MC 4 R in diet induced obesity may indicate increased alpha MSH secretion in an attempt to limit overeating . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
The aim of this study was to identify structural requirements in both ligand and receptor that determine gamma melanocyte stimulating hormone ( MSH ) selectivity for the MC3R versus the MC4R . ^^^ Substitution of Asp 10 in [ Nle 4 ] Lys gamma 2 MSH for Gly 10 from [ Nle 4 ] alpha MSH , increased both activity and affinity for the MC4R while the MC3R remained unaffected . ^^^ Analysis of chimeric MC3R / MC4Rs and mutant MC4Rs showed that Tyr 268 of the MC4R mainly determined the low affinity for [ Nle 4 ] Lys gamma 2 MSH . ^^^ This is supported by mutagenesis of Tyr 268 to Ile in the MC4R which increased affinity and activity for [ Nle 4 ] Lys gamma 2 MSH , but decreased affinity for two peptides with constrained cyclic structure of the melanocortin core sequence , MT 2 and [ D Tyr 4 ] MT 2 , that also displayed lower affinity for the MC3R . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Compared with [ Ahx 4 ] alpha MSH , the linear MTII designated as alpha MSH ND revealed a preference for the MC4R , whereas its IC 50 and EC 50 values were comparable to those of MTII reported previously . ^^^ Meanwhile , maximum cAMP generating activity was observed at a higher concentration ( 10 ( 5 ) M ) of alpha MSH ND ( 6 10 ) , and MC4R preference was changed into MC3R preference . ^^^ Replacement of the His 6 residue of alpha MSH ND by Gln , Asn , Arg or Lys decreased not only the receptor binding , but also the cAMP generating activity in both the MC3R and the MC4R . ^^^ The structure of [ Gln 6 ] alpha MSH ND exhibited a stable type 1 ' beta turn comprising Asp 5 , Gln 6 , D Phe 7 and Arg 8 . [ Lys 6 ] alpha MSH ND showed a greatly reduced binding affinity and cAMP generating activity with the loss of MC4R selectivity . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
We have shown that alpha MSH , desacetyl alpha MSH and beta MSH bound to the MC 3 R and MC 4 R with similar affinity and stimulated cAMP with similar potency in HEK 293 cells transfected with MC 3 R and MC 4 R . ^^^ In contrast gamma ( 2 ) MSH showed selectivity for the MC 3 R over the MC 4 R both in binding affinity and cAMP stimulation . alpha MSH and beta MSH injected ICV into fasted rats at doses of 1 , 3 and 6 nmol resulted in a decrease in food intake , ( 2 h food intake : alpha MSH 6 nmol , 1 . 7+ / 0 . 3 g ; beta MSH 6 nmol , 1 . 5+ / 0 . 3 g vs . saline 6 . 0+ / 0 . 5 g , P < 0 . 001 ) . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
OBJECTIVE : To search for mutations in melanocortin pathway elements , that is , the melanocortin 4 receptor ( MC4R ) , agouti related protein ( AGRP ) , and ( alpha melanocyte stimulating hormone ( alpha MSH ) genes in children with severe obesity . ^^^ STUDY DESIGN : Direct sequencing of the MC4R encoding sequence and single strand polymorphism conformation analysis of AGRP and alpha MSH genes were performed in 63 severely obese children . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
High affinity binding sites were demonstrated in the GT 1 1 and GT 1 7 cells for NDP alpha melanocyte stimulating hormone ( MSH ; K ( 1 ) = 1 . 1 10 10 ( 10 ) and 1 . 8 10 10 ( 10 ) M ) and agouti related protein ( AGRP ; K ( 1 ) = 1 . 548 10 10 ( 9 ) and 1 . 663 ( 9 ) M ) . alpha MSH stimulated cAMP production in GT 1 1 cells with an EC ( 50 ) of 2 . 2 10 10 ( 8 ) M , and cAMP production was inhibited in the presence of AGRP , an endogenous antagonist of the MC 4 R . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
We investigated which hypothalamic areas known to express MC4R are involved in the regulation of feeding by using alpha melanocyte stimulating hormone ( alpha MSH ) , an endogenous MC4R agonist , and agouti related peptide ( Agrp ) , an endogenous MC4R antagonist . ^^^ This study indicates that the hypothalamic nuclei expressing MC4R vary in their sensitivity to Agrp and alpha MSH with regard to their effect on feeding . . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Further mutational analysis of this region of MC4R demonstrated that Tyr ( 268 ) was required for the selective interaction with Agouti protein , because a profound loss of the ability of Agouti protein to inhibit ( 125 ) 1 labeled [ Nle ( 4 ) , d Phe ( 7 ) ] alpha melanocyte stimulating hormone ( MSH ) binding was observed by the single mutation of Tyr ( 268 ) to Ile . ^^^ This same residue conferred selectivity for the MC4R selective agonist , [ d Tyr ( 4 ) ] MT 2 , whereas it inhibited interaction with the MC3R selective agonist , [ Nle ( 4 ) ] Lys gamma ( 2 ) MSH . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
RESULTS : Among the several analogues examined , [ Gln ( 6 ) ] alpha melanocyte stimulating hormone ( MSH ) ND was found to have 10000 times less biological activity than alpha MSH ND for the MC1R , whereas , the potencies of both oligopeptides were comparable in both the melanocortin 3 receptor ( MC3R ) and MC4R . [ Gln ( 6 ) ] alpha MSH ND exhibited a type 1 ' beta turn that was similar to the type 1 beta turn structure of alpha MSH ND . ^^^ By homology modeling analysis , the His ( 6 ) of alpha MSH ND was found to interact with the TM 2 regions of all three receptors ( Glu ( 94 ) of MC1R , Glu ( 94 ) of MC3R , and Glu ( 100 ) of MC4R ) , but [ Gln ( 6 ) ] alpha MSH ND did not . ^^^ The phenyl ring of the D Phe ( 7 ) residue of [ Gln ( 6 ) ] alpha MSH ND revealed an interaction with the TM 3 regions of both the MC3R and MC4R ( Ser ( 122 ) of MC3R or Ser ( 127 ) of MC4R ) . ^^^ This is a possible explanation for the biological activity of [ Gln ( 6 ) ] alpha MSH ND for the MC1R being significantly lower than that for either the MC3R or MC4R . ^^^ CONCLUSIONS : Minimization of the MC1R selectivity whilst preserving its comparable potency for both the MC3R and MC4R could be achieved by modifying the D Phe ( 7 ) orientation of alpha MSH ND , while maintaining the ' type 1 beta turn ' like structure . . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
No high affinity binding sites for NEI were detected on B 16 melanoma cells and there was no significant displacement of [ 1251 ] alpha MSH by MCH , NEI or NGE with MC 3 R , MC 4 R and MC 5 R expressed in COS cells . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
MSH : a functional ligand that regulated energy homeostasis via hypothalamic MC 4 R . alpha Melanocyte stimulating hormone ( MSH ) has generally been assumed to be the endogenous ligand acting at the melanocortin 4 receptor ( MC 4 R ) , activation of which in the hypothalamus leads to reduced feeding . ^^^ However , beta MSH is also capable of activating MC 4 R and inhibiting feeding . ^^^ Here , we investigated the possibility that beta MSH acts as an endogenous MC 4 R agonist and that this melanocortin peptide plays a role in the regulation of feeding and energy balance . ^^^ We found that beta MSH had significantly higher affinities than alpha MSH at both human MC 4 R transfected into CHO cells ( K ( 1 ) : beta MSH , 11 . 4+ / 0 . 4 nmol / l versus alpha MSH , 324+ / 16 nmol / l , P < 0 . 001 ) and MC 4 R in rat hypothalamic homogenates ( K ( 1 ) : beta MSH , 5 . 0+ / 0 . 4 nmol / l versus alpha MSH , 22 . 5+ / 2 . 3 nmol / l , P < 0 . 001 ) . ^^^ These sites match the distribution of beta MSH immunoreactive fibres and also the distribution of MC 4 R binding sites which we and others previously reported . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
The central melanocortin system consists of alpha MSH , agouti related protein ( AGRP ) , MC3R and MC4R . ^^^ AGRP and alpha MSH are believed to be the natural antagonist and agonist respectively of MC3R and MC4R . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
Agouti related protein ( AgRP ( 83 132 ) ) , a known endogenous MC3R and MC4R antagonist , did not reduce the stimulation of prolactin mRNA expression by gamma 3 MSH or Ala ( 8 ) gamma 2 MSH . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
The melanocortin receptor 4 ( MC 4 R ) plays the most important role in mediating catabolic effects of alpha MSH . ^^^ In this review , we present a series of own studies on NPY , insulin and MSH / ACTH4 10 , an MC 4 R agonist . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
We evaluated the effects of intracerebroventricular ( i . c . v . ) administration of IL 1beta ( 30 ng ) and melanocortin receptor agonists : alpha MSH , an MC3 / MC4 R agonist ( 0 . 2 microg ) or gamma MSH , an MC 3 R agonist ( 2 microg ) or HS 014 , an MC 4 R antagonist ( 2 microg ) , on an elevated plus maze ( EPM ) test . ^^^ These data suggest that alpha MSH , through central MC 4 R can modulate the anxiety like behavior induced by IL 1beta . . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
In vitro functional studies of variants T112M , S127L , and I226T supported a pathogenic role of the S127L mutation , because signaling properties of the receptor in response to the MC4R agonists alpha MSH , beta MSH , and gamma ( 1 ) MSH were impaired . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NDP alpha MSH induced a time dependent internalization of MC 4 R that was partially prevented by AgRP . ^^^
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and P32245	Pubmed	SVM Score :0.0
NA