Subtype-specific role of phospholipase C-β in bradykinin and LPA signaling through differential binding of different PDZ scaffold proteins
| Autor: | Yong Ryul Yang, Seyoung Lim, Jung Woong Choi, Pann-Ghill Suh, Sung Ho Ryu, Yun-Hee Kim, Yong-Seok Oh, Eung Kyun Kim, Jung Kuk Kim, Kyun Heo, Sun-Hee Kim, Jaeyoon Kim |
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| Rok vydání: | 2010 |
| Předmět: |
Scaffold protein
Sodium-Hydrogen Exchangers PDZ domain Phospholipase C beta PDZ Domains Cell Cycle Proteins Biology Bradykinin Isozyme Receptors G-Protein-Coupled chemistry.chemical_compound Lysophosphatidic acid Humans Gene silencing Receptor Adaptor Proteins Signal Transducing Cell Proliferation G protein-coupled receptor Phospholipase C Membrane Proteins Cell Biology Phosphoproteins Cell biology Biochemistry chemistry Gene Knockdown Techniques Calcium Lysophospholipids HeLa Cells Signal Transduction |
| Zdroj: | Cellular Signalling. 22:1153-1161 |
| ISSN: | 0898-6568 |
| DOI: | 10.1016/j.cellsig.2010.03.010 |
| Popis: | Among phospholipase C (PLC) isozymes (beta, gamma, delta, epsilon, zeta and eta), PLC-beta plays a key role in G-protein coupled receptor (GPCR)-mediated signaling. PLC-beta subtypes are often overlapped in their distribution, but have unique knock-out phenotypes in organism, suggesting that each subtype may have the different role even within the same type of cells. In this study, we examined the possibility of the differential coupling of each PLC-beta subtype to GPCRs, and explored the molecular mechanism underlying the specificity. Firstly, we found that PLC-beta1 and PLC-beta 3 are activated by bradykinin (BK) or lysophosphatidic acid (LPA), respectively. BK-triggered phosphoinositides hydrolysis and subsequent Ca(2+) mobilization were abolished specifically by PLC-beta1 silencing, whereas LPA-triggered events were by PLC-beta 3 silencing. Secondly, we showed the evidence that PDZ scaffold proteins is a key mediator for the selective coupling between PLC-beta subtype and GPCR. We found PAR-3 mediates physical interaction between PLC-beta1 and BK receptor, while NHERF2 does between PLC-beta 3 and LPA(2) receptor. Consistently, the silencing of PAR-3 or NHERF2 blunted PLC signaling induced by BK or LPA respectively. Taken together, these data suggest that each subtype of PLC-beta is selectively coupled to GPCR via PDZ scaffold proteins in given cell types and plays differential role in the signaling of various GPCRs. |
| Databáze: | OpenAIRE |
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