Structural and compositional determinants of cortistatin activity

Criado, José R.; Li, Haitao; Jiang, Xiaohui; Spina, Mariarosa; Huitrón‐Reséndiz, Salvador; Liapakis, George; Calbet, Marta; Siehler, Sandra; Henriksen, Steven J.; Koob, George; Hoyer, Daniel; Sutcliffe, J. Gregor; Goodman, Murray; Lecea, Luı́s de

doi:10.1002/(sici)1097-4547(19990615)56:6<611::aid-jnr7>3.0.co;2-g

Cited by 43 publications

(14 citation statements)

References 41 publications

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“…Structure-activity relationship studies on the cortistatin peptide show that the extracyclic N-terminal proline and the C-terminal lysine amide are essential for its distinct biological properties (19). This suggests that both of these residues are required for binding of cortistatin to its specific receptor.…”

Section: Discussionmentioning

confidence: 99%

MrgX2 Is a High Potency Cortistatin Receptor Expressed in Dorsal Root Ganglion

Robas

Mead

Fidock

2003

Journal of Biological Chemistry

222

187

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MrgX2 is a recently identified orphan G-protein-coupled receptor whose ligand and physiological function were unknown. Here we describe cortistatin, a neuropeptide for which no specific receptor has been identified previously, as a high potency ligand at MrgX2. Cortistatin has several biological functions including roles in sleep regulation, locomotor activity, and cortical function. Using a "reverse pharmacology" approach, we have identified a number of additional cyclic peptide agonists for MrgX2, determined their rank order of potency, and demonstrated that this receptor has a pharmacological profile distinct from the other characterized members of the Mrg (Mas-related genes) family. In MrgX2-expressing cells, cortistatin-stimulated increases in intracellular Ca 2؉ but had no effect on basal or forskolin-stimulated cAMP levels, suggesting that this receptor is G q -coupled. Immunohistochemical and quantitative PCR studies show MrgX2 to have a limited expression profile, both peripheral and within the central nervous system, with highest levels in dorsal root ganglion.

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Section: Discussionmentioning

confidence: 99%

MrgX2 Is a High Potency Cortistatin Receptor Expressed in Dorsal Root Ganglion

Robas

Mead

Fidock

2003

Journal of Biological Chemistry

222

187

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“…Structure-activity relationship studies have indicated that the Pro moiety at position 2 and the C-terminal Lys residue are crucial for the distinctive effects of CST in the brain (Criado et al 1999). Based on these data, the existence of specific CST receptors able to bind selectively to CST but not to SS1 has been postulated.…”

Section: Uts2r5mentioning

confidence: 99%

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

Tostivint¹,

Daza²,

Bergqvist³

et al. 2014

Journal of Molecular Endocrinology

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Somatostatin (SS) and urotensin II (UII) are members of two families of structurally related neuropeptides present in all vertebrates. They exert a large array of biological activities that are mediated by two families of G-protein-coupled receptors called SSTR and UTS2R respectively. It is proposed that the two families of peptides as well as those of their receptors probably derive from a single ancestral ligand-receptor pair. This pair had already been duplicated before the emergence of vertebrates to generate one SS peptide with two receptors and one UII peptide with one receptor. Thereafter, each family expanded in the three whole-genome duplications (1R, 2R, and 3R) that occurred during the evolution of vertebrates, whereupon some local duplications and gene losses occurred. Following the 2R event, the vertebrate ancestor is deduced to have possessed three SS (SS1, SS2, and SS5) and six SSTR (SSTR1-6) genes, on the one hand, and four UII (UII, URP, URP1, and URP2) and five UTS2R (UTS2R1-5) genes, on the other hand. In the teleost lineage, all these have been preserved with the exception of SSTR4. Moreover, several additional genes have been gained through the 3R event, such as SS4 and a second copy of the UII, SSTR2, SSTR3, and SSTR5 genes, and through local duplications, such as SS3. In mammals, all the genes of the SSTR family have been preserved, with the exception of SSTR6. In contrast, for the other families, extensive gene losses occurred, as only the SS1, SS2, UII, and URP genes and one UTS2R gene are still present.

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“…A c c e p t e d M a n u s c r i p t 9 As indicated above, previous studies show that CST has a high affinity for the different human sst subtypes in stably transfected cell lines (Criado et al, 1999). The expression of two other known receptors capable of binding CST, MrgX2 and GHS-R, in the immune system is a less explored field.…”

Section: Page 9 Of 20mentioning

confidence: 99%

“…The SRIF receptor genes are all located on different chromosomes, but have a high degree of sequence homology (Patel et al, 1996). CST binds with high affinity to all 5 sst subtypes (Criado et al, 1999;Fukusumi et al, 1997;Siehler et al, 1998). The function of SRIF has been studied far more in depth: it can act as a neurotransmitter and neurohormone and in peripheral tissues it regulates endocrine and exocrine secretion and acts as a modulator of motor activity in the gastrointestinal tract (Reichlin, 1983a;Reichlin, 1983b).…”

Section: Introductionmentioning

confidence: 99%

The role of cortistatin in the human immune system

Hagen

Dalm

Staal

et al. 2008

Molecular and Cellular Endocrinology

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Please cite this article as: van Hagen, P.M., Dalm, V.A., Staal, F., Hofland, L.J., The Role of Cortistatin in the Human Immune System, Molecular and Cellular Endocrinology (2007Endocrinology ( ), doi:10.1016Endocrinology ( /j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractCortistatin (CST) is a recently described neuropeptide that shares high homology with somatostatin (somatotropin release-inhibiting factor, SRIF) and binds with high affinity to all somatostatin receptor (sst) subtypes. CST is currently known to have a widespread distribution in many human organs including the immune system. The activities specific to CST may be partially attributable to its binding to the growth hormone secretagogue (GHS) receptor (GHS-R) and the orphan Gprotein-coupled receptor MrgX2. Human immune cells produce CST, whereas macrophage lineage and activated endothelium express sst 2 , and human lymphocytes express sst 3 . The human thymus expresses sst 1,2,3 , MrgX2 and almost all immune cells express GHS-R. Moreover, at this very moment promising research with CST in experimental animal models is being performed. On the basis of these promising results, studies aiming to further evaluate the possibilities of CST as a therapeutic agent in human immune mediated inflammatory diseases are warranted.

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Structural and compositional determinants of cortistatin activity

Cited by 43 publications

References 41 publications

MrgX2 Is a High Potency Cortistatin Receptor Expressed in Dorsal Root Ganglion

MrgX2 Is a High Potency Cortistatin Receptor Expressed in Dorsal Root Ganglion

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

The role of cortistatin in the human immune system

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