PDZ Domain-containing 1 (PDZK1) Protein Regulates Phospholipase C-β3 (PLC-β3)-specific Activation of Somatostatin by Forming a Ternary Complex with PLC-β3 and Somatostatin Receptors

Kim, Jung Kuk; Kwon, Ohman; Kim, Jin-Ho; Kim, Eung Kyun; Park, Hye Kyung; Lee, Ji Eun; Kim, Kyung Lock; Choi, Jong Seob; Lim, Seyoung; Seok, Heon; Lee-Kwon, Whaseon; Choi, Jang Hyun; Kang, Byoung Heon; Kim, Sanguk; Ryu, Sung Ho; Suh, Pann Ghill

doi:10.1074/jbc.m111.337865

Cited by 27 publications

(22 citation statements)

References 64 publications

(64 reference statements)

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“…Nevertheless, PDZK1 has been implicated in regulating a subset of GPCRs. PDZK1 promotes the formation of a complex between SSTRs and PLCb3, similar to what is observed for LPA 2 R (Oh et al, 2004;Choi et al, 2010), thereby facilitating somatostatinstimulated PLC activation, Ca 21 mobilization, and ERK1/2 phosphorylation (Kim et al, 2012). PDZK1 also functions to enhance human prostacyclin receptor (hIPR) cell surface localization and cAMP signaling and contributes to endothelial cell migration and angiogenesis (Turner et al, 2011).…”

Section: Membrane-associated Guanylate Kinase With Inverted Orientatimentioning

confidence: 68%

PDZ Protein Regulation of G Protein–Coupled Receptor Trafficking and Signaling Pathways

Dunn

Ferguson

2015

Mol Pharmacol

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G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacological strategies for the treatment of human pathologies. Of the many GPCR-interacting proteins, postsynaptic density protein of 95 kilodaltons, disc large, zona occludens-1 (PDZ) domain-containing proteins appear most abundant and have similarly been implicated in disease mechanisms. PDZ proteins play an important role in regulating receptor and channel protein localization within synapses and tight junctions and function to scaffold intracellular signaling protein complexes. In the current study, we review the known functional interactions between PDZ domain-containing proteins and GPCRs and provide insight into the potential mechanisms of action. These PDZ domain-containing proteins include the membraneassociated guanylate-like kinases [postsynaptic density protein of 95 kilodaltons; synapse-associated protein of 97 kilodaltons; postsynaptic density protein of 93 kilodaltons; synapse-associated protein of 102 kilodaltons; discs, large homolog 5; caspase activation and recruitment domain and membrane-associated guanylate-like kinase domain-containing protein 3; membrane protein, palmitoylated 3; calcium/calmodulin-dependent serine protein kinase; membrane-associated guanylate kinase protein (MAGI)-1, MAGI-2, and MAGI-3], Na 1 /H 1 exchanger regulatory factor proteins (NHERFs) (NHERF1, NHERF2, PDZ domaincontaining kidney protein 1, and PDZ domain-containing kidney protein 2), Golgi-associated PDZ proteins (Ga-binding protein interacting protein, C-terminus and CFTR-associated ligand), PDZ domain-containing guanine nucleotide exchange factors (GEFs) 1 and 2, regulator of G protein signaling (RGS)-homology-RhoGEFs (PDZ domain-containing RhoGEF and leukemia-associated RhoGEF), RGS3 and RGS12, spinophilin and neurabin-1, SRC homology 3 domain and multiple ankyrin repeat domain (Shank) proteins (Shank1, Shank2, and Shank3), partitioning defective proteins 3 and 6, multiple PDZ protein 1, Tamalin, neuronal nitric oxide synthase, syntrophins, protein interacting with protein kinase C a 1, syntenin-1, and sorting nexin 27.

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Section: Membrane-associated Guanylate Kinase With Inverted Orientatimentioning

confidence: 68%

PDZ Protein Regulation of G Protein–Coupled Receptor Trafficking and Signaling Pathways

Dunn

Ferguson

2015

Mol Pharmacol

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“…RERG was reported as a prognostic marker in breast cancer, whose expression correlated inversely proliferation, patient survival, and development of distant metastases (48). It has been reported that PDZK1 forms a complex linking somatostatin receptors and phospholipase C-b (PLC-b), necessary for somatostatin physiologic responses (49). Although further studies are warranted, epigenetic silencing of RDBP in metastatic PPGL may cause global changes in chromatin and/or gene transcription, possibly affecting expression of genes (e.g., JUNB, PDZK1, RERG, GPX3) involved with response to apoptotic stimuli and invasion, proliferation, and metabolism.…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation Profiling in Pheochromocytoma and Paraganglioma Reveals Diagnostic and Prognostic Markers

Cubas

Korpershoek

Inglada-Pérez

et al. 2015

Clinical Cancer Research

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Purpose: Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors, associated with highly variable postoperative evolution. The scarcity of reliable PPGL prognostic markers continues to complicate patient management. In this study, we explored genome-wide DNA methylation patterns in the context of PPGL malignancy to identify novel prognostic markers.Experimental Design: We retrospectively investigated DNA methylation patterns in PPGL with and without metastases using high-throughput DNA methylation profiling data (Illumina 27K) from two large, well-characterized discovery (n ¼ 123; 24 metastatic) and primary validation (n ¼ 154; 24 metastatic) series. Additional validation of candidate CpGs was performed by bisulfite pyrosequencing in a second independent set of 33 paraffin-embedded PPGLs (19 metastatic).Results: Of the initial 86 candidate CpGs, we successfully replicated 52 (47 genes), associated with metastatic PPGL. Of these, 48 CpGs showed significant associations with time to progression even after correcting for SDHB genotype, suggesting their value as prognostic markers independent of genetic background. Hypermethylation of RDBP (negative elongation factor complex member E) in metastatic tumors was further validated by bisulfite pyrosequencing [Db metastatic-benign ¼ 0.29, P ¼ 0.003; HR, 1.4; 95% confidence interval (CI), 1.1-2.0; P ¼ 0.018] and may alter transcriptional networks involving (RERG, GPX3, and PDZK1) apoptosis, invasion, and maintenance of DNA integrity.Conclusions: This is the first large-scale study of DNA methylation in metastatic PPGL that identifies and validates prognostic markers, which could be used for stratifying patients according to risk of developing metastasis. Of the three CpGs selected for further validation, one (RDBP) was clearly confirmed and could be used for stratifying patients according to the risk of developing metastases. Clin Cancer Res; 21(13); 3020-30. Ó2015 AACR.

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“…PDZK1 belongs to the family of Na + /H + exchange regulatory factors which comprises four members: NHERF1-4 with NHERF3 also known as PDZK1. NHERFs have been reported to regulate the function of several GPCRs including the parathyroid 1 receptor, somatostatin receptors 1-5 (SSTRs), human prostacyclin receptor (hIPR), β 2 -adrenergic receptor (β 2 AR), metabotropic glutamate receptor 5, purinergic P2Y1 receptor, CCR5 chemokine receptor and κ opioid receptor [29,[42][43][44][45][46]. CRFR1 and the 5-HT 2A R represent the fourth and fifth GPCRs that have been shown to interact with PDZK1.…”

Section: Discussionmentioning

confidence: 99%

PDZK1/NHERF3 Differentially Regulates Corticotropin-releasing Factor Receptor 1 and Serotonin 2A Receptor Signaling and Endocytosis

Walther¹,

Caetano²,

Dunn

et al. 2015

Cellular Signalling

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PDZ Domain-containing 1 (PDZK1) Protein Regulates Phospholipase C-β3 (PLC-β3)-specific Activation of Somatostatin by Forming a Ternary Complex with PLC-β3 and Somatostatin Receptors

Cited by 27 publications

References 64 publications

PDZ Protein Regulation of G Protein–Coupled Receptor Trafficking and Signaling Pathways

PDZ Protein Regulation of G Protein–Coupled Receptor Trafficking and Signaling Pathways

DNA Methylation Profiling in Pheochromocytoma and Paraganglioma Reveals Diagnostic and Prognostic Markers

PDZK1/NHERF3 Differentially Regulates Corticotropin-releasing Factor Receptor 1 and Serotonin 2A Receptor Signaling and Endocytosis

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