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PDZ interactions between PHLPP phosphatases and the NHERF scaffold
Author(s) -
Kunkel Maya,
Garcia Erin L,
Hall Randy A,
Newton Alexandra C
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.761.26
Subject(s) - pdz domain , scaffold protein , microbiology and biotechnology , protein phosphatase 1 , chemistry , phosphorylation , protein–protein interaction , phosphatase , biology , signal transduction
The PHLPP family of serine/threonine protein phosphatases plays a critical role in regulating the balance between cell survival and apoptosis. The PHLPP family consists of three members, the N‐terminal alternative splice variants, PHLPP1α and PHLPP1β, and PHLPP2, a separate gene product. All isozymes contain a type I PDZ‐binding motif at their C‐terminus: TPL for PHLPP1 and TAL for PHLPP2. We sought to identify potential PDZ domain‐containing proteins that scaffold these phosphatases in order to elucidate differences in PHLPP1 and PHLPP2 signaling at spatially restricted locations within the cell. Using a proteomic array containing 96 purified PDZ domains, we have identified domains that interact with the 25 C‐terminal residues of PHLPP1 and PHLPP2. Specifically, we have observed that the PDZ ligands of both PHLPP1 and PHLPP2 can interact with the scaffold proteins NHERF‐1 and NHERF‐2. In live cells, addition of the last 10 residues of PHLPP1 or PHLPP2 to cyan fluorescent protein (CFP) is sufficient to relocalize CFP to NHERF‐1 or NHERF‐2. However, NHERF‐dependent relocalization is only observed for full‐length PHLPP2; full‐length PHLPP1 is in a conformation in which the C‐terminus is not available to interact with the NHERF PDZ domains. These results suggest differential signaling by PHLPP2 versus PHLPP1 at the NHERF scaffold. This work was supported by NIH P01 DK54441