Synthesis and function of 3-phosphorylated inositol lipids.
The 3-phosphorylated inositol lipids fulfill roles as second messengers by interacting with the lipid binding domains of a variety of cellular proteins. Such interactions can affect the subcellular localization and aggregation of target proteins, and through allosteric effects, their activity. Generation of 3-phosphoinositides has been documented to influence diverse cellular pathways and hence alter a spectrum of fundamental cellular activities. This review is focused on the 3-phosphoinositide lipids, the synthesis of which is acutely triggered by extracellular stimuli, the enzymes responsible for their synthesis and metabolism, and their cell biological roles. Much knowledge has recently been gained through structural insights into the lipid kinases, their interaction with inhibitors, and the way their 3-phosphoinositide products interact with protein targets. This field is now moving toward a genetic dissection of 3-phosphoinositide action in a variety of model organisms. Such approaches will reveal the true role of the 3-phosphoinositides at the organismal level in health and disease.
Vanhaesebroeck
B
B
Ludwig Institute for Cancer Research, Riding House Street, London W1W 7BS. bartvanh@ludwig.ucl.ac.uk
Leevers
S J
SJ
Ahmadi
K
K
Timms
J
J
Katso
R
R
Driscoll
P C
PC
Woscholski
R
R
Parker
P J
PJ
Waterfield
M D
MD
D019870:1-Phosphatidylinositol 4-Kinase / Q000737:chemistry / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000730:Androstadienes / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001665:Binding Sites; D001798:Blood Proteins / Q000737:chemistry; D020134:Catalytic Domain; D002455:Cell Division / Q000502:physiology; D002867:Chromones / Q000737:chemistry / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry* / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000737:chemistry / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins / Q000737:chemistry; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000077191:Wortmannin
D019870:1-Phosphatidylinositol 4-Kinase; D000199:Actins; D000730:Androstadienes; D001798:Blood Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010716:Phosphatidylinositols; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins; D010744:Phosphoric Monoester Hydrolases; D025521:Tumor Suppressor Proteins; D000077191:Wortmannin; C039077:platelet protein P47; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494929:PTEN protein, human