Wednesday 29 October 2003
second messenger in signal transduction
Many cell-surface receptors induce production of second messengers like PIP3 (phosphatidylinositol 3,4,5-trisphosphate) that convey signals to the cytoplasm from the cell surface.
PIP3 signals activates the kinase PDK1 (3-phosphoinositide-dependent protein kinase-1), which in turn activates the kinase AKT, also known as protein kinase B (PKB).
Proteins phosphorylated by activated AKT promote cell survival.
Phosphorylation of Ikappa-B kinase leads to activation of the transcription factor NF-kB to oppose apoptosis. Bad is a protein in the Bcl-2 gene family that opposes Bcl-2 to induce apoptosis. Phosphorylation of Bad by AKT blocks anti-apoptotic activity to promote cell survival.
Similarly, phosphorylation of the protease caspase 9 or forkhead transcription factors by AKT block the induction of apoptosis by these factors. AKT promotes cell survival and opposes apoptosis by a variety of routes. (Biocarta)
PI3K/PTEN/AKT signaling pathway
Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov. 2005 Dec;4(12):988-1004. PMID: #16341064#
Schulz I, Krause E. Inositol 1,4,5-trisphosphate and its co-players in the concert of Ca2+ signalling—new faces in the line up. Curr Mol Med. 2004 May;4(3):313-22. PMID: #15101688#
Irvine RF. 20 years of Ins(1,4,5)P3, and 40 years before. Nat Rev Mol Cell Biol. 2003 Jul;4(7):586-90. PMID: #12838341#