Journal
EMBO JOURNAL
Volume 25, Issue 4, Pages 910-920Publisher
WILEY
DOI: 10.1038/sj.emboj.7600979
Keywords
cancer; EBP50; NHERF; PDGFR; PTEN
Categories
Funding
- NCI NIH HHS [CA09299-26, CA107201, CA16672, R01 CA107201, P30 CA016672, T32 CA009299] Funding Source: Medline
Ask authors/readers for more resources
PTEN, a tumor suppressor frequently inactivated in many human cancers, directly antagonizes the activity of phosphatidylinositol-3- OH kinase ( PI3K) by dephosphorylating phosphoinositides. We show here that PTEN interacts directly with the NHERF1 and NHERF2 ( Na (+)/ H (+) exchanger regulatory factor) homologous adaptor proteins through the PDZ motif of PTEN and the PDZ1 domain of NHERF1 or both PDZ domains of NHERF2. NHERFs were shown to interact directly with platelet- derived growth factor receptor ( PDGFR), and we demonstrate the assembly of a ternary complex between PTEN, NHERFs and PDGFR. The activation of the PI3K pathway after PDGFR stimulation was prolonged in NHERF1( -/ -) mouse embryonic fibroblasts as compared to wild- type cells, consistent with defective PTEN recruitment to PDGFR in the absence of NHERF1. Depletion of NHERF2 by small interfering RNA similarly increased PI3K signaling. Phenotypically, the loss of NHERF1 enhanced the PDGF-induced cytoskeletal rearrangements and chemotactic migration of the cells. These data indicate that, in normal cells, NHERF proteins recruit PTEN to PDGFR to restrict the activation of the PI3K.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available