title: 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.
abstract: Phospholipase C-β (PLC-β) is a key molecule in G protein-coupled receptor (GPCR)-mediated signaling. Many studies have shown that the four PLC-β subtypes have different physiological functions despite their similar structures. Because the PLC-β subtypes possess different PDZ-binding motifs, they have the potential to interact with different PDZ proteins. In this study, we identified PDZ domain-containing 1 (PDZK1) as a PDZ protein that specifically interacts with PLC-β3. To elucidate the functional roles of PDZK1, we next screened for potential interacting proteins of PDZK1 and identified the somatostatin receptors (SSTRs) as another protein that interacts with PDZK1. Through these interactions, PDZK1 assembles as a ternary complex with PLC-β3 and SSTRs. Interestingly, the expression of PDZK1 and PLC-β3, but not PLC-β1, markedly potentiated SST-induced PLC activation. However, disruption of the ternary complex inhibited SST-induced PLC activation, which suggests that PDZK1-mediated complex formation is required for the specific activation of PLC-β3 by SST. Consistent with this observation, the knockdown of PDZK1 or PLC-β3, but not that of PLC-β1, significantly inhibited SST-induced intracellular Ca(2+) mobilization, which further attenuated subsequent ERK1/2 phosphorylation. Taken together, our results strongly suggest that the formation of a complex between SSTRs, PDZK1, and PLC-β3 is essential for the specific activation of PLC-β3 and the subsequent physiologic responses by SST.
authors.affiliation: Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Jung Kuk
authors.initials: JK
authors.lastname: Kim
authors.forename: Ohman
authors.initials: O
authors.lastname: Kwon
authors.forename: Jinho
authors.initials: J
authors.lastname: Kim
authors.forename: Eung-Kyun
authors.initials: EK
authors.lastname: Kim
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Park
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Kyung Lock
authors.initials: KL
authors.lastname: Kim
authors.forename: Jung Woong
authors.initials: JW
authors.lastname: Choi
authors.forename: Seyoung
authors.initials: S
authors.lastname: Lim
authors.forename: Heon
authors.initials: H
authors.lastname: Seok
authors.forename: Whaseon
authors.initials: W
authors.lastname: Lee-Kwon
authors.forename: Jang Hyun
authors.initials: JH
authors.lastname: Choi
authors.forename: Byoung Heon
authors.initials: BH
authors.lastname: Kang
authors.forename: Sanguk
authors.initials: S
authors.lastname: Kim
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
mesh_terms: D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D054799:Phospholipase C beta / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; C484659:PDZK1 protein, human; D017481:Receptors, Somatostatin; D013004:Somatostatin; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054799:Phospholipase C beta; D002118:Calcium