Pertussis toxin-sensitive Gi/o proteins are involved in nerve growth factor-induced pro-survival Akt signaling cascade in PC12 cells

Wu, Eddy H.T.; Wong, Yung Hou

doi:10.1016/j.cellsig.2004.11.008

Cited by 33 publications

(31 citation statements)

References 47 publications

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“…To reveal the involvement of G i/o proteins in a particular signaling pathway, pertussis toxin (PTX) is an indispensable tool since the toxin catalyzes the ADP-ribosylation of G i/o proteins and abolish their ability to become activated [78] . As mentioned in the above section, it has been demonstrated that PTX-sensitive G i family members are involved in NGF-regulated activation of Akt and phosphorylation of tuberin [29,73] . Moreover, there have been several recent reports of GPCR-mediated activation of Akt.…”

Section: Mechanisms Of Tuberin Regulation By Gpcrsmentioning

confidence: 99%

“…These findings further reveal and strengthen the important connection between G i/o protein signaling and NGF-induced tuberin regulation. [67,73] ( fig. 3 ).…”

Section: Regulation Of Tuberin By Rtksmentioning

confidence: 99%

“…Not surprisingly, a diverse range of G i -coupled receptors are capable of regulating tuberin. For example, all three opioid receptor subtypes ( ␦ , , ), ␣ 2 -adrenoceptor, and muscarinic M 4 receptor are capable of inducing the phosphorylation of tuberin in both transfected and native cellular models [29,30,73] . Tuberin is rapidly phosphorylated in response to the G i -coupled receptor agonists.…”

Section: Mechanisms Of Tuberin Regulation By Gpcrsmentioning

confidence: 99%

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

Wu²,

Wong³

2006

Neurosignals

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Tuberin, a tumor suppressor protein, is involved in various cellular functions including survival, proliferation, and growth. It has emerged as an important effector regulated by receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs). Regulation of tuberin by RTKs and GPCRs is highly complex and dependent on the type of receptors and their associated signaling molecules. Apart from Akt, the first kinase recognized to phosphorylate and inactivate tuberin upon growth factor stimulation, an increasing number of kinases upstream of tuberin have been identified. Furthermore, recruitment of different scaffolding adaptor components to the activated receptors appears to play an important role in the regulation of tuberin activity. More recently, the differential regulation of tuberin by various G protein family members have also been intensively studied, it appears that G proteins can both facilitate (e.g., G_i/o) as well as inhibit (e.g., G_q) tuberin phosphorylation. In the present review, we attempt to summarize our emerging understandings of the roles of RTKs, GPCRs, and their cross-talk on the regulation of tuberin.

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Section: Mechanisms Of Tuberin Regulation By Gpcrsmentioning

confidence: 99%

“…These findings further reveal and strengthen the important connection between G i/o protein signaling and NGF-induced tuberin regulation. [67,73] ( fig. 3 ).…”

Section: Regulation Of Tuberin By Rtksmentioning

confidence: 99%

Section: Mechanisms Of Tuberin Regulation By Gpcrsmentioning

confidence: 99%

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

Wu²,

Wong³

2006

Neurosignals

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“…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].…”

Section: The Functions Of G Protein Signaling In Neuronal Differentiamentioning

confidence: 96%

“…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).…”

Section: The Functions Of G Protein Signaling In Neuronal Differentiamentioning

confidence: 99%

G protein signaling controls the differentiation of multiple cell lineages

Wang¹,

Wong²

2009

BioFactors

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G protein‐coupled receptors (GPCRs) detect a great diversity of extracellular stimuli ranging from hormonal peptides, chemokines, neurotransmitters, lipids, nucleotides, amino acids, biogenic amines to ions. G protein‐coupled pathways regulate a rich collection of biological processes involved in normal physiological function of the body as well as in pathological progression of diseases. In addition to their function in postmitotic steady‐state tissues, GPCRs have been implicated in the differentiation of stem cells and tissue specific progenitor cells during development. Examples of these include the functions of nucleotides and neuropeptides in neuronal differentiation and axon growth, chemokines in lymphocyte differentiation and activation, and other GPCR‐mediated processes in the differentiation of adipocytes, osteoblasts and smooth muscle cells. This review summarizes the recent advances in our understanding of the importance of GPCR‐linked signaling cascades in the differentiation of different cell lineages. © 2009 International Union of Biochemistry and Molecular Biology, Inc.

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Activation of ras‐dependent signaling pathways by G₁₄‐coupled receptors requires the adaptor protein TPR1

Kwan

Yung

et al. 2012

J of Cellular Biochemistry

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Many G(q) -coupled receptors mediate mitogenic signals by stimulating extracellular signal-regulated protein kinases (ERKs) that are typically regulated by the small GTPase Ras. Recent studies have revealed that members of the Gα(q) family may possess the ability to activate Ras/ERK by interacting with the adaptor protein tetratricopeptide repeat 1 (TPR1). Within the Gα(q) family, the highly promiscuous Gα(14) can relay signals from numerous receptors. Here, we examined if Gα(14) interacts with TPR1 to stimulate Ras signaling pathways. Expression of the constitutively active Gα(14) QL mutant in HEK293 cells led to the formation of GTP-bound Ras as well as increased phosphorylations of downstream signaling molecules including ERK and IκB kinase. Stimulation of endogenous G(14) -coupled somatostatin type 2 and α(2) -adrenergic receptors produced similar responses in human hepatocellular HepG2 carcinoma cells. Co-immunoprecipitation assays using HEK293 cells demonstrated a stronger association of TPR1 for Gα(14) QL than Gα(14) , suggesting that TPR1 preferentially binds to the GTP-bound form of Gα(14) . Activated Gα(14) also interacted with the Ras guanine nucleotide exchange factors SOS1 and SOS2. Expression of a dominant negative mutant of TPR1 or siRNA-mediated knockdown of TPR1 effectively abolished the ability of Gα(14) to induce Ras signaling in native HepG2 or transfected HEK293 cells. Although expression of the dominant negative mutant of TPR1 suppressed Gα(14) QL-induced phosphorylations of ERK and IκB kinase, it did not affect Gα(14) QL-induced stimulation of phospholipase Cβ or c-Jun N-terminal kinase. Our results suggest that TPR1 is required for Gα(14) to stimulate Ras-dependent signaling pathways, but not for the propagation of signals along Ras-independent pathways.

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Pertussis toxin-sensitive Gi/o proteins are involved in nerve growth factor-induced pro-survival Akt signaling cascade in PC12 cells

Cited by 33 publications

References 47 publications

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

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

G protein signaling controls the differentiation of multiple cell lineages

Activation of ras‐dependent signaling pathways by G₁₄‐coupled receptors requires the adaptor protein TPR1

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Pertussis toxin-sensitive Gi/o proteins are involved in nerve growth factor-induced pro-survival Akt signaling cascade in PC12 cells

Cited by 33 publications

References 47 publications

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

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

G protein signaling controls the differentiation of multiple cell lineages

Activation of ras‐dependent signaling pathways by G14‐coupled receptors requires the adaptor protein TPR1

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Activation of ras‐dependent signaling pathways by G₁₄‐coupled receptors requires the adaptor protein TPR1