Journal
JOURNAL OF CELL SCIENCE
Volume 118, Issue 20, Pages 4605-4612Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.02637
Keywords
ceramide 1-phosphate; ceramide kinase; sphingosine 1-phosphate; sphingosine kinase; inflammation; cancer
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Funding
- NCI NIH HHS [R01CA61774] Funding Source: Medline
- NCRR NIH HHS [1C06RR17393] Funding Source: Medline
- NHLBI NIH HHS [R01 HL072925] Funding Source: Medline
- NIAID NIH HHS [R01AI50094] Funding Source: Medline
- NIGMS NIH HHS [R37GM043880] Funding Source: Medline
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The phosphorylated sphingolipid metabolites sphingosine I-phosphate (SIP) and ceramide 1-phosphate (C1P) have emerged as potent bioactive agents. Recent studies have begun to define new biological functions for these lipids. Generated by sphingosine kinases and ceramide kinase, they control numerous aspects of cell physiology, including cell survival and mammalian inflammatory responses. Interestingly, SIP is involved in cyclooxygenase-2 induction and C1P is required for the activation and translocation of cPLA(2). This suggests that these two sphingolipid metabolites may act in concert to regulate production of eicosanoids, important inflammatory mediators. Whereas SIP functions mainly via G-protein-coupled receptors, C1P appears to bind directly to targets such as cPLA(2) and protein phosphatase 1/2A. SIP probably also has intracellular targets, and in plants it appears to directly regulate the G protein alpha subunit GPA1.
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