Fpk1/2 kinases regulate cellular sphingoid long-chain base abundance and alter cellular resistance to LCB elevation or depletion

Yukari Yamane-Sando, Etsuko Shimobayashi, Mitsugu Shimobayashi, Yasunori Kozutsumi, Shogo Oka, Hiromu Takematsu

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Sphingolipids are a family of eukaryotic lipids biosynthesized from sphingoid long-chain bases (LCBs). Sphingolipids are an essential class of lipids, as their depletion results in cell death. However, acute LCB supplementation is also toxic; thus, proper cellular LCB levels should be maintained. To characterize the "sphingolipid-signaling intercross," we performed a kinome screening assay in which budding yeast protein kinase-knockout strains were screened for resistance to ISP-1, a potent inhibitor of LCB biosynthesis. Here, one pair of such DIR (deletion-mediated ISP-1 resistance) genes, FPK1 and FPK2, was further characterized. Cellular LCB levels increased in the fpk1/2{increment} strain, which was hypersensitive to phytosphingosine (PHS), a major LCB species of yeast cells. Concomitantly, this strain acquired resistance to ISP-1. Fpk1 and Fpk2 were involved in two downstream events; that is, ISP-1 uptake due to aminophospholipid flippase and LCB degradation due to LCB4 expression. RSK3, which belongs to the p90-S6K subfamily, was identified as a functional counterpart of Fpk1/2 in mammalian cells as the RSK3 gene functionally complemented the ISP-1-resistant phenotype of fpk1/2{increment} cells.

Original languageEnglish
Pages (from-to)196-212
Number of pages17
JournalMicrobiologyOpen
Volume3
Issue number2
DOIs
Publication statusPublished - 04-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Microbiology

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