Involvement of G_i/oProteins in Nerve Growth Factor-Stimulated Phosphorylation and Degradation of Tuberin in PC-12 Cells and Cortical Neurons

Abstract

Book reviews 67The place of these important tools for medical practice, education and research and as aids to the enlightenment of patients is well explained and fully expressedThe authors have carried out an excellent, timely and scholarly review of iatrogenic illness. It is my hope that they will examine in a subsequent book such topics as commerciogenic medical harm (marketing of medicines and infant formula) mediogenic medical harm (premature proclamation of "breakthroughs" and unbalanced scare stories) political medical harm (subordination of health care to weaponry, and medical involvement with torture), and ideological medical harm (denial of medical care to women, sanctity of life, abortion, euthanasia, terminal care).

Tuberin: A Stimulus-Regulated Tumor Suppressor Protein Controlled by a Diverse Array of Receptor Tyrosine Kinases and G Protein-Coupled Receptors

“…Recruited PI3K would in turn stimulate Akt phosphorylation and activation [41,42] . Eventually, tuberin would be phosphorylated by activated Akt, disassociated from its binding partners and degraded via a proteasomal mechanism [29,43] . The mechanisms by which Akt-mediated phosphorylation of tuberin that lead to the degradation and functional inactivation of tuberin remain unclear.…”

“…Apart from demonstrating the role of tuberin in the regulation of cell growth and proliferation, results from several laboratories over the past few years have provided new insights into how tuberin might affect cell survival, cell adhesion, cell morphology, cell migration, neuronal differentiation, regulation of cellular energy, post-Golgi transport, or protein trafficking in the cell [29][30][31][32][33][34][35] . A particularly interesting feature of tuberin is the presence of multiple serine, threonine and tyrosine phosphorylation sites [36,37] , suggesting that the functional activity of tuberin could be potentially regulated by different signaling molecules.…”

G protein signaling controls the differentiation of multiple cell lineages

“…These include the findings that demonstrate the localization of GPCRs and their signaling components in lipid rafts and caveolae [63], dimerization of GPCRs [64], and trans-activation of receptor tyrosine kinases by GPCRs [65]. In the case of cell differentiation, examples of novel GPCR signaling mechanism include transactivation of TrkA by purinergic P2Y2 receptor [12], and mediation of partial NGF signaling by G i/o proteins [14,17,18]. With new discoveries in the signaling mechanisms of GPCRs and novel ligands for orphan receptors, we will undoubtedly appreciate the significance of G protein-linked signaling in the differentiation of various cell lineages and development of tissues and organs.…”

“…Signaling through G i/o -coupled muscarinic acetylcholine receptors appears to cooperate with NGF in activating the PI3K/Akt pathway and promoting neuronal survival [14][15][16]. Treatment of PC12 cells with pertussis toxin (PTX; which inactivates G i/o ) reduced NGF-induced Akt phosphorylation, but has no effect on the Akt response elicited by epidermal growth factor (EGF).…”

“…Treatment of PC12 cells with pertussis toxin (PTX; which inactivates G i/o ) reduced NGF-induced Akt phosphorylation, but has no effect on the Akt response elicited by epidermal growth factor (EGF). The induction of PI3K/Akt pathway by NGF is in part mediated through the Gβγ subunit released from activated G i/o , which promotes the phosphorylation of translation regulator tuberlin to enhance neuronal survival [14,15]. In a similar manner, G i/o mediates part of the NGF-induced p38 and JNK phosphorylations, which are required for neuronal differentiation [17,18].…”