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Phosphatase Activity of the Fungal Adenylate Cyclase Cyr1, the Yeast Homologue of PHLPP
Author(s) -
Grzechnik Agnieszka Teresa,
Petty Emily,
Pillus Lorraine,
Newton Alexandra C
Publication year - 2016
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.30.1_supplement.1141.1
Subject(s) - biology , microbiology and biotechnology , phosphatase , phosphorylation
PH domain Leucine Rich Repeat Protein Phosphatases (PHLPP) suppress survival signaling by at least two mechanisms: dephosphorylating AGC kinases, such as Akt, and regulating the epigenome by suppressing histone phosphorylation. Interestingly, the only adenylate cyclase encoded in the Saccharomyces cerevisiae genome, CYR1 , has a previously uncharacterized amino‐terminal segment homologous to PHLPP. Here we use biochemical, molecular, and genetic techniques to characterize the PHLPP‐associated phosphatase activity in yeast. Specifically, we show that overexpression of Cyr1 results in reduced phosphorylation of substrates such as Ser10 on Histone H3. The segment of Cyr1 that is homologous to PHLPP comprises a Leucine Rich Repeat (LRR) segment and a Serine/Threonine PP2C phosphatase domain, but lacks the PH domain and C‐terminal PDZ ligand of mammalian PHLPP. Thus, the ability of Cyr1 to suppress histone phosphorylation supports studies with mammalian PHLPP showing that the LRR segment is critical for its epigenetic function. Our study establishes that Cyr1 contains a previously undescribed phosphatase function, and suggests a functional link between cAMP‐dependent signaling and PHLPP. Support or Funding Information A.T.G. was supported in part by the UCSD Graduate Training Program in Cellular and Molecular Pharmacology through an institutional training grant from the National Institute of General Medical Sciences, T32 GM007752. Additionally, this work was supported by NIH Grant GM067946 (to A.C.N.)