Signalling functions for sphingolipid long-chain bases in Saccharomyces cerevisiae

Over the past several years, studies of sphingolipid functions in the baker's yeast Saccharomyces cerevisiae have revealed that the sphingoid LCBs (long-chain bases), dihydrosphingosine and PHS (phytosphingosine), are important signalling molecules or second messengers under heat stress and during non-stressed conditions. LCBs are now recognized as regulators of AGC-type protein kinase (where AGC stands for protein kinases A, G and C) Pkh1 and Pkh2, which are homologues of mammalian phosphoinositide-dependent protein kinase 1. LCBs were previously shown to activate Pkh1 and Pkh2, which then activate the downstream protein kinase Pkc1. We have recently demonstrated that PHS stimulates Pkh1 to activate additional downstream kinases including Ypk1, Ypk2 and Sch9. We have also found that PHS acts downstream of Pkhl and partially activates Ypk1, Ypk2 and Sch9. These kinases control a wide range of cellular processes including growth, cell wall integrity, stress resistance, endocytosis and aging. As we learn more about the cellular processes controlled by Ypk1, Ypk2 and Sch9, we will have a far greater appreciation of LCBs as second messengers.