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Query: UNIPROT:P01185 (
vasopressin
)
23,126
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Vasopressin controls water balance largely through PKA-dependent effects to regulate the collecting duct water channel aquaporin-2 (AQP2). Although considerable information has accrued regarding the regulation of water and solute transport in collecting duct cells, information is sparse regarding the signaling connections between PKA and transport responses. Here, we exploited recent advancements in protein mass spectrometry to perform a comprehensive, multiple-replicate analysis of changes in the phosphoproteome of native rat inner medullary collecting duct cells in response to the vasopressin V2 receptor-selective agonist 1-desamino-8D-arginine vasopressin. Of the 10,738 phosphopeptides quantified, only 156 phosphopeptides were significantly increased in abundance, and only 63 phosphopeptides were decreased, indicative of a highly selective response to
vasopressin
. The list of upregulated phosphosites showed several general characteristics:
1
) a preponderance of sites with basic (positively charged) amino acids arginine (R) and lysine (K) in position -2 and -3 relative to the phosphorylated amino acid, consistent with phosphorylation by PKA and/or other basophilic kinases;
2
) a greater-than-random likelihood of sites previously demonstrated to be phosphorylated by PKA;
3
) a preponderance of sites in membrane proteins, consistent with regulation by membrane association; and
4
) a greater-than-random likelihood of sites in proteins with class I COOH-terminal PDZ ligand motifs. The list of downregulated phosphosites showed a preponderance of those with
proline
in position +1 relative to the phosphorylated amino acid, consistent with either downregulation of
proline
-directed kinases (e.g., MAPKs or cyclin-dependent kinases) or upregulation of one or more protein phosphatases that selectively dephosphorylate such sites (e.g., protein phosphatase 2A). The phosphoproteomic data were used to create a web resource for the investigation of G protein-coupled receptor signaling and regulation of AQP2-mediated water transport.
...
PMID:Phosphoproteomic identification of vasopressin V2 receptor-dependent signaling in the renal collecting duct. 3131 56
The oxytocin-arginine vasopressin (OT-AVP) ligand-receptor family influences a variety of physiological, behavioral, and social behavioral processes in the brain and periphery. The OT-AVP family is highly conserved in mammals, but recent discoveries have revealed remarkable diversity in OT ligands and receptors in New World Monkeys (NWMs) providing a unique opportunity to assess the effects of genetic variation on pharmacological signatures of peptide ligands. The consensus mammalian OT sequence has leucine in the 8
th
position (Leu
8
-OT), whereas a number of NWMs, including the marmoset, have
proline
in the 8
th
position (Pro
8
-OT) resulting in a more rigid tail structure. OT and AVP bind to OT's cognate G-protein coupled receptor (OTR), which couples to various G-proteins (G
i/o
, G
q
, G
s
) to stimulate diverse signaling pathways. CHO cells expressing marmoset (mOTR), titi monkey (tOTR), macaque (qOTR), or human (hOTR) OT receptors were used to compare AVP and OT analog-induced signaling. Assessment of G
q
-mediated increase in intracellular calcium (Ca
2+
) demonstrated that AVP was less potent than OT analogs at OTRs from species whose endogenous ligand is Leu
8
-OT (tOTR, qOTR, hOTR), relative to Pro
8
-OT. Likewise, AVP-induced membrane hyperpolarization was less potent at these same OTRs. Evaluation of (Ca
2+
)-activated potassium (K
+
) channels using the inhibitors apamin, paxilline, and TRAM-34 demonstrated that both intermediate and large conductance Ca
2+
-activated K
+
channels contributed to membrane hyperpolarization, with different pharmacological profiles identified for distinct ligand-receptor combinations. Understanding more fully the contributions of structure activity relationships for these peptide ligands at
vasopressin
and OT receptors will help guide the development of OT-mediated therapeutics.
...
PMID:Comparison of the pharmacologic profiles of arginine vasopressin and oxytocin analogs at marmoset, titi monkey, macaque, and human oxytocin receptors. 3201 19
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