NHERF2 increases platelet-derived growth factor-induced proliferation through PI-3-kinase/Akt-, ERK-, and Src family kinase-dependent pathway
SCIE
SCOPUS
- Title
- NHERF2 increases platelet-derived growth factor-induced proliferation through PI-3-kinase/Akt-, ERK-, and Src family kinase-dependent pathway
- Authors
- Kang, YJ; Jeon, ES; Lee, HJ; Oh, YS; Suh, PG; Jung, JS; Donowitz, M; Kim, JH
- Date Issued
- 2004-07
- Publisher
- ELSEVIER SCIENCE INC
- Abstract
- Platelet-derived growth factor (PDGF) has multiple functions including inhibition of apoptosis and promotion of cell proliferation. In this study. we show that Na+/H+ exchanger regulatory factor 2 (NHERF2) binds to the carboxyl-terminal PDZ domain-binding motif of the PDGF receptor through a PDZ domain-mediated interaction, and evaluate the consequence on PDGF-induced proliferation. Stable transfection with NHERF2 increased the PDGF-induced phosphorylation of ERK and Akt in Ratl embryonic fibroblasts. The phosphorylation of Akt was blocked by pretreatment with LY294002, a PI-3-kinase inhibitor, in both Rat1/NHERF2 and Rat1/vector cells. In Rat1/vector cells, PDGF-induced phosphorylation of ERK was completely inhibited by pretreatment with PD98059, a MEK inhibitor. In contrast, the NHERF2-dependent increase of ERK phosphorylation was not affected by pretreatment with PD98059 in Rat1/NHERF2 cells. Thus, the NHERF2dependent increase of ERK phosphorylation occurs in a MEK-independent fashion. Pretreatment with PP2, a specific inhibitor of Src family tyrosine kinase, completely blocked the NHERF2-dependent increase of the phosphorylation of ERK and Akt, suggesting that NHERF2 upregulates Erk phosphorylation through a Src family kinase-dependent pathway. Consistent with these results, the PDGF-induced thymidine incorporation was increased in Rat1/NHERF2 cells, and the NHERF2-dependent increase of thymidine incorporation was prevented by treatment with LY294002 and PP2 but not with PD98059. These results suggest that NHERF2 stimulates PDGF-induced proliferation by increasing PI-3-kinase/Akt, MEKindependent ERK, and Src family kinase-mediated signaling pathways. (C) 2004 Elsevier Inc. All rights reserved.
- Keywords
- PDGF; NHERF2; PDZ; proliferation; MEK; Src; EXCHANGER REGULATORY FACTOR; PDZ-CONTAINING PROTEINS; NA+/H+ EXCHANGER-3; SIGNAL-TRANSDUCTION; ACTIN CYTOSKELETON; NHE3 KINASE; ACTIVATION; RECEPTOR; PDGF; REQUIRES
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/17940
- DOI
- 10.1016/j.cellsig.2003.12.003
- ISSN
- 0898-6568
- Article Type
- Article
- Citation
- CELLULAR SIGNALLING, vol. 16, no. 7, page. 791 - 800, 2004-07
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- There are no files associated with this item.
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