Phosphoinositide 3-kinase signaling pathways

Cantrell, D.A., 2001, Phosphoinositide 3-kinase signaling pathways. J. Cell Science, 114 1439-1445. 

Brader S, Eccles SA (2004) Phosphoinositide 3-kinase signalling pathways in tumor progression, invasion and angiogenesis. Tumori 90 2-8... 

Maffucci T, Cooke FT, Foster FM, Traer CJ, Fry MJ, Falasca M. Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration. J Cell Biol 2005 169(5) 789-799. 

Manning, B. D., and Cantley, L. C. (2003). United at last The tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signaling. Biochem. Soc. Trans. 31, 573-578. 

Martelli, A., Nyakern, M., Tabellini, G., Bortul, R., Tazzari, P., Evangelisti, C. and Cocco, L. (2006) Phosphoinositide 3 kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia. Leukemia 20, 911-928. 

With its multiple second messengers and protein kinases, the phosphoinositide signaling pathway is much more complex than the cAMP pathway. For example, different cell types may contain one or more specialized calcium- and calmodulin-dependent kinases with limited substrate specificity (eg, myosin light-chain kinase) in addition to a general calcium- and calmodulin-... 

The Ca2+-phosphoinositide signaling pathway. Key proteins include hormone receptors (R), a G protein (G), a phosphoinositide-specific phospholipase C (PLC), protein kinase C substrates of the kinase (S), calmodulin (CaM), and calmodulin-binding enzymes (E), including kinases, phosphodiesterases, etc. (PIP2, phosphatidylinositol-4,5-bisphosphate DAG, diacylglycerol. Asterisk denotes activated state. Open arrows denote regulatory effects.)... 

Zhao, H., Sapolsky, R. M., and Steinberg, G. K. (2006). Phosphoinositide-3-kinase/Akt survival signal pathways are implicated in neuronal survival after stroke. Mol. Neurobiol. 34, 249—269. 

Figure 5.1 The PIP3 signaling pathway obtained from the Alliance for Cell Signaling [177], Proteins are illustrated as circles and non-protein molecules as triangles. Arrows indicate the direction of information flow in the network, including phosphorylation reactions, such as the phosphorylation of PI to PI(4)P, which is catalyzed by phosphoinositide 4-kinase (PI4K), and allosteric activations indicated by arrows with + signs.

A particularly important connection between signalling pathways controlled by heterotrimeric and monomeric G proteins is chemotaxis. Chemotactic signals are received by G-protein-coupled receptors and transmitted by Py-subunits of heterotrimeric G proteins, notably to phosphoinositide 3-kinase (Ptdins 3-kinase) and phospholipase C. Finally, monomeric G proteins direct the signal to the cytoskeleton, promoting crawling and rolling of cells (see discussion of the role of phosphoinositides for the orientation of the cell towards stimuli in Chapter 4). 

PLC)/Ca, and PKC signaling pathways in rat neutrophils [352]. Activation of phosphoinositide 3-kinase (PI3K) and Src family kinase is required for the respiratory burst in rat neutrophils stimulated with... 

Hou L, Klann E. 2004. Activation of the phosphoinositide 3-kinase-akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression. J Neurosci 24 6352-6361. 

In previous sections, we have seen how signal transduction from cytokine receptors and receptor tyrosine kinases (RTKs) begins with formation of multiprotein complexes associated with the plasma membrane. Here we discuss how these receptors initiate signaling pathways that Involve membrane-bound phosphorylated inositol lipids, collectively referred to as phosphoinositides. We begin with the branch of the phospholnositide pathway that also is mediated by G protein-coupled receptors and then consider another branch that is not shared with these receptors. 

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