Journal
BIOESSAYS
Volume 35, Issue 7, Pages 602-611Publisher
WILEY-BLACKWELL
DOI: 10.1002/bies.201200176
Keywords
PH domain; phosphoinositides; PI 3-kinase; signal transduction
Categories
Funding
- NIH [5T32 GM007491, GM55692, PO1 CA 100324]
- National Research Service Award [1 F31 AG040932-01]
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Class I PI 3-kinases signal by producing the signaling lipid phosphatidylinositol(3,4,5) trisphosphate, which in turn acts by recruiting downstream effectors that contain specific lipid-binding domains. The class I PI 3-kinases comprise four distinct catalytic subunits linked to one of seven different regulatory subunits. All the class I PI 3-kinases produce the same signaling lipid, PIP3, and the different isoforms have overlapping expression patterns and are coupled to overlapping sets of upstream activators. Nonetheless, studies in cultured cells and in animals have demonstrated that the different isoforms are coupled to distinct ranges of downstream responses. This review focuses on the mechanisms by which the production of a common product, PIP3, can produce isoform-specific signaling by PI 3-kinases.
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