Sphingolipid-mediated Signal Transduction

Upon various insults or stresses, sphingomyelinase activity (SMase, in mammalian cells) or inositol-sphingolipid-cleaving enzyme activity (in S. cerevisiae) are induced to increase cellular ceramide level to bring appropriate biological responses. Many experimental evidences suggest that sphingolipids are essential for survival of an organism under stressful conditions.

in mammalian cells

TNF alpha
Fas
IL-1
NGF
Vitamin D3
gamma Irradiation
Reactive oxygen species
Etoposide
Daunorubicin
Lytosine arabinoside
Gemcitabine

in S. cerevisiae

Heat
High osmolarity
Other stresses

Apoptosis
Cell cycle arrest
Angiogenesis
Senescense
Inflammation

Neutral, Mg-dependent plasma membrane SMase (NSMase)
Neutral, Mg-independent intracellular SMase
Acidic, Mg-independent lysosomal SMase (ASMase)
Acidic, Zn-dependent secretary SMase

Ceramidase Family

Alkalne ceramidase
Alkaline phytoceramidase
Alkaline dihydroceramidase
Lysosomal acid ceramidase
Neutral mitochondrial ceramidase

Sphingsoine Kinase Family

Sphingosine Kinase 1
Sphingosine Kinase 2

Inositol phosphoceramide: IPC
Mannose inositol phosphoceramide: MIPC
Mannose diinositol phosphoceramide: M(IP)2C


Yeast has phytosphingosine and phytoceramide instead of sphingosine and ceramide, respectively.


Phytosphingsoine, dihyrdosphingosine, and their phosphates, and ceramides are signaling molecular for yeast growth, cell cycle regulation, and heat stress responses.