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Aurora Kinase A (AURKA) Regulates the Vacuolar H + ‐ATPase (V‐ATPase) in Kidney Carcinoma Cells
Author(s) -
Albataineh Mohammad M.,
Alzamora Rodrigo,
Gong Fan,
Marciszyn Allison L.,
Hallows Kenneth R.,
PastorSoler Nuria M.
Publication year - 2013
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.27.1_supplement.1210.16
Subject(s) - v atpase , activator (genetics) , atpase , ampk , kinase , protein subunit , chemistry , microbiology and biotechnology , phosphorylation , cancer research , protein kinase a , biology , enzyme , biochemistry , receptor , gene
The V‐ATPase mediates kidney H + secretion and is involved in metastasis. V‐ATPase A subunit phosphorylation at Ser175 is important for PKA‐mediated V‐ATPase activity in intercalated cells (ICs). The metabolic sensor AMP‐activated kinase (AMPK) prevents V‐ATPase apical accumulation by PKA in ICs. We hypothesized that AURKA overexpressed by aggressive carcinomas regulates the V‐ATPase in human kidney carcinoma cells (Caki‐2) via Ser‐175. AURKA is abnormally expressed in Caki‐2 cell cytoplasm and phosphorylates the V‐ATPase A subunit at Ser175 in vitro and in Caki‐2 cells. Higher pSer175 was detected from cells transfected with WT A subunit and treated with an AURKA activator, compared to untreated cells, and compared to cells expressing an S175A A‐subunit mutant. Caki‐2 cell immunolabeling revealed that an AURKA activator induced marked V‐ATPase membrane accumulation in cell projections compared to untreated cells. AURKA activation enhanced the rate of wound healing in Caki‐2 cells compared to untreated cells. AMPK activation blocked the AURKA‐induced effects on V‐ATPase membrane accumulation and wound healing. AURKA‐mediated V‐ATPase regulation may have a role in the metastatic potential of kidney carcinomas and may represent a potential therapeutic target. Supported by NIDDK.