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EPHB2 MTOR (1 - 13 of 13)
PMID: 15757502
Activation of protein synthesis in cardiomyocytes by the hypertrophic agent phenylephrine requires the activation of ERK and involves phosphorylation of tuberous sclerosis complex 2 (TSC2).
... that ERK is also required for ... of mTOR signalling ...   (details)

EPHB2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 15757502

Activation of protein synthesis in cardiomyocytes by the hypertrophic agent phenylephrine requires the activation of ERK and involves phosphorylation of tuberous sclerosis complex 2 (TSC2).
Source

The Biochemical journal (6/15/2005)

Abstract

Activation of protein synthesis in cardiomyocytes by the hypertrophic agent phenylephrine requires the activation of ERK and involves phosphorylation of tuberous sclerosis complex 2 (TSC2). The hypertrophic Gq-protein-coupled receptor agonist PE (phenylephrine) activates protein synthesis. We showed previously that activation of protein synthesis by PE requires MEK [MAPK (mitogen-activated protein kinase) /ERK (extracellular-signal-regulated kinase) kinase] and mTOR (mammalian target of rapamycin). However, it remained unclear whether ERK activation was required and which downstream components were involved in activating mTOR and protein synthesis. Using an adenovirus encoding the MKP3 (MAPK phosphatase 3) to inhibit ERK activity, we demonstrate that ERK is essential for the activation of protein synthesis by PE. Activation and phosphorylation of S6K1 (ribosomal protein S6 kinase 1) and phosphorylation of eIF4E (eukaryotic initiation factor 4E) -binding protein (both are mTOR targets) were also inhibited by MKP3, suggesting that ERK is also required for the activation of mTOR signalling. PE stimulation of cardiomyocytes induced the phosphorylation of TSC2 (tuberous sclerosis complex 2), a negative regulator of mTOR activity. TSC2 was phosphorylated only weakly at Thr1462, but phosphorylated at additional sites within the sequence RXRXX (S/T). This differs from the phosphorylation induced by insulin, indicating that MEK/ERK signalling targets distinct sites in TSC2. This phosphorylation may be mediated by p90RSK (90 kDa ribosomal protein S6K), which is activated by ERK, and appears to involve phosphorylation at Ser1798. Activation of protein synthesis by PE is partially insensitive to the mTOR inhibitor rapamycin. Inhibition of the MAPK-interacting kinases by CGP57380 decreases the phosphorylation of eIF4E and PE-induced protein synthesis. Moreover, CGP57380+rapamycin inhibited protein synthesis to the same extent as blocking ERK activation, suggesting that MAPK-interacting kinases and regulation of mTOR each contribute to the activation of protein synthesis by PE in cardiomyocytes.

PMID: 16183639
Glutamatergic regulation of the p70S6 kinase in primary mouse neurons.
... of ERK1/2 but ... the activation of mTOR-S6K; ...   (details)

EPHB2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 16183639

Glutamatergic regulation of the p70S6 kinase in primary mouse neurons.
Source

The Journal of biological chemistry (11/18/2005)

Abstract

Glutamatergic regulation of the p70S6 kinase in primary mouse neurons. Brief glutamatergic stimulation of neurons from fetal mice, cultured in vitro for 6 days, activates the mTOR-S6 kinase, ERK1/2 and Akt pathways, to an extent approaching that elicited by brain-derived neurotrophic factor. In contrast, sustained glutamatergic stimulation inhibits ERK, Akt, and S6K. Glutamatergic activation of S6K is calcium/calmodulin-dependent and is prevented by inhibitors of calcium/calmodulin-dependent protein kinase 2, phosphatidylinositol 3-OH-kinase and by rapamycin. 2-Amino-5-phosphonovaleric acid, an inhibitor of N'-methyl-D-aspartate receptors, abolishes glutamatergic activation of ERK1/2 but not the activation of mTOR-S6K; the latter is completely abolished by inhibitors of voltage-dependent calcium channels. Added singly, dopamine gives slight, and norepinephrine a more significant, activation of ERK and S6K; both catecholeamines, however, enhance glutamatergic activation of S6K but not ERK. After 12 days in culture, the response to direct glutamatergic activation is attenuated but can be uncovered by suppression of gamma-aminobutyric acid interneurons with bicuculline in the presence of the weak K (+) channel blocker 4-aminopyridine (4-AP). This selective synaptic activation of mTOR-S6K is also resistant to APV and inhibited by Ca (2+) channel blockers and higher concentrations of glutamate. Elongation factor 2 (EF2) is phosphorylated and inhibited by the eEF2 kinase (CaM kinase III); the latter is inhibited by the S6K or Rsk. Bicuculline/4-AP or KCl-induced depolarization reduces, whereas higher concentrations of glutamate increases, EF2 phosphorylation. Thus the mTOR-S6K pathway in neurons, a critical component of the late phase of LTP, is activated by glutamatergic stimulation in a calcium/calmodulin-dependent fashion through a calcium pool controlled by postsynaptic voltage-dependent calcium channels, whereas sustained stimulation of extrasynaptic glutamate receptors is inhibitory.

PMID: 17255101
p21-activated kinase 1 is activated through the mammalian target of rapamycin/p70 S6 kinase pathway and regulates the replication of hepatitis C virus in human hepatoma cells.
... that mTOR is regulated by ... and ERK.   (details)

EPHB2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 17255101

p21-activated kinase 1 is activated through the mammalian target of rapamycin/p70 S6 kinase pathway and regulates the replication of hepatitis C virus in human hepatoma cells.
Source

The Journal of biological chemistry (4/20/2007)

Abstract

p21-activated kinase 1 is activated through the mammalian target of rapamycin/p70 S6 kinase pathway and regulates the replication of hepatitis C virus in human hepatoma cells. Cellular mechanisms that regulate the replication of hepatitis C virus (HCV) RNA are poorly understood. p21-activated kinase 1 (PAK1) is a serine/threonine kinase that has been suggested to participate in antiviral signaling. We studied its role in the cellular control of HCV replication. Transfection of PAK1-specific small interfering RNA enhanced viral RNA and protein abundance in established replicon cell lines as well as cells infected with chimeric genotype 1a/2a HCV, despite reducing cellular proliferation, suggesting specific regulation of HCV replication. PAK1 knockdown did not reduce interferon regulatory factor 3-dependent gene expression, indicating that this regulation is independent of the retinoic acid-inducible gene I/interferon regulatory factor 3 pathway. On the other hand, LY294002 and rapamycin abolished PAK1 phosphorylation and enhanced HCV abundance, suggesting that the mammalian target of rapamycin (mTOR) is involved in PAK1 regulation of HCV. Small interfering RNA knockdown of the mTOR substrate p70 S6 kinase abrogated PAK1 phosphorylation and enhanced HCV RNA abundance, whereas overexpression of a constitutively active alternate substrate, eukaryotic translation initiation factor 4E-binding protein 1, increased cap-independent viral translation and viral RNA abundance without influencing PAK1 phosphorylation. Similar data indicated that mTOR is regulated by both phosphatidylinositol 3-kinase/Akt and ERK. Taken together, the data indicate that p70 S6 kinase activates PAK1 and contributes to phosphatidylinositol 3-kinase- and ERK-mediated regulation of HCV RNA replication.

PMID: 17537959
Mitogen-activated protein kinase upregulates the dendritic translation machinery in long-term potentiation by controlling the mammalian target of rapamycin pathway.
... ERK mediated the ... of mTOR by ...   (details)

EPHB2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 17537959

Mitogen-activated protein kinase upregulates the dendritic translation machinery in long-term potentiation by controlling the mammalian target of rapamycin pathway.
Source

The Journal of neuroscience : the official journal of the Society for Neuroscience (5/30/2007)

Abstract

Mitogen-activated protein kinase upregulates the dendritic translation machinery in long-term potentiation by controlling the mammalian target of rapamycin pathway. Protein synthesis is required for persistent forms of synaptic plasticity, including long-term potentiation (LTP). A key regulator of LTP-related protein synthesis is mammalian target of rapamycin (mTOR), which is thought to modulate translational capacity by facilitating the synthesis of particular components of the protein synthesis machinery. Recently, extracellularly regulated kinase (ERK) also was shown to mediate plasticity-related translation, an effect that may involve regulation of the mTOR pathway. We studied the interaction between the mTOR and ERK pathways in hippocampal LTP induced at CA3-CA1 synapses by high-frequency synaptic stimulation (HFS). Within minutes after HFS, the expression of multiple translational proteins, the synthesis of which is under the control of mTOR, increased in area CA1 stratum radiatum. This upregulation was detected in pyramidal cell dendrites and was blocked by inhibitors of the ERK pathway. In addition, ERK mediated the stimulation of mTOR by HFS. The possibility that ERK regulates mTOR by acting at a component further upstream in the phosphatidylinositide 3-kinase (PI3K) -mTOR pathway was tested by probing the phosphorylation of p90-S6 kinase, phosphoinositide-dependent kinase 1 (PDK1), and Akt. ERK inhibitors blocked HFS-induced phosphorylation of all three proteins at sites implicated in the regulation of mTOR. Moreover, a component of basal and HFS-induced ERK activity depended on PI3K, indicating that mTOR-mediated protein synthesis in LTP requires coincident and mutually dependent activity in the PI3K and ERK pathways. The role of ERK in regulating PDK1 and Akt, with their extensive effects on cellular function, has important implications for the coordinated response of the neuron to LTP-inducing stimulation.

... that ERK regulates mTOR by ...   (details)

EPHB2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 17537959

Mitogen-activated protein kinase upregulates the dendritic translation machinery in long-term potentiation by controlling the mammalian target of rapamycin pathway.
Source

The Journal of neuroscience : the official journal of the Society for Neuroscience (5/30/2007)

Abstract

Mitogen-activated protein kinase upregulates the dendritic translation machinery in long-term potentiation by controlling the mammalian target of rapamycin pathway. Protein synthesis is required for persistent forms of synaptic plasticity, including long-term potentiation (LTP). A key regulator of LTP-related protein synthesis is mammalian target of rapamycin (mTOR), which is thought to modulate translational capacity by facilitating the synthesis of particular components of the protein synthesis machinery. Recently, extracellularly regulated kinase (ERK) also was shown to mediate plasticity-related translation, an effect that may involve regulation of the mTOR pathway. We studied the interaction between the mTOR and ERK pathways in hippocampal LTP induced at CA3-CA1 synapses by high-frequency synaptic stimulation (HFS). Within minutes after HFS, the expression of multiple translational proteins, the synthesis of which is under the control of mTOR, increased in area CA1 stratum radiatum. This upregulation was detected in pyramidal cell dendrites and was blocked by inhibitors of the ERK pathway. In addition, ERK mediated the stimulation of mTOR by HFS. The possibility that ERK regulates mTOR by acting at a component further upstream in the phosphatidylinositide 3-kinase (PI3K)-mTOR pathway was tested by probing the phosphorylation of p90-S6 kinase, phosphoinositide-dependent kinase 1 (PDK1), and Akt. ERK inhibitors blocked HFS-induced phosphorylation of all three proteins at sites implicated in the regulation of mTOR. Moreover, a component of basal and HFS-induced ERK activity depended on PI3K, indicating that mTOR-mediated protein synthesis in LTP requires coincident and mutually dependent activity in the PI3K and ERK pathways. The role of ERK in regulating PDK1 and Akt, with their extensive effects on cellular function, has important implications for the coordinated response of the neuron to LTP-inducing stimulation.

PMID: 18215133
The binding of PRAS40 to 14-3-3 proteins is not required for activation of mTORC1 signalling by phorbol esters/ERK.
... for activation of mTORC1 signalling ... phorbol esters/ERK.   (details)

EPHB2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  mTORC1   (MLST8   RPTOR   MTOR )

PMID: 18215133

The binding of PRAS40 to 14-3-3 proteins is not required for activation of mTORC1 signalling by phorbol esters/ERK.
Source

The Biochemical journal (4/1/2008)

Abstract

The binding of PRAS40 to 14-3-3 proteins is not required for activation of mTORC1 signalling by phorbol esters/ERK. PRAS40 binds to the mTORC1 (mammalian target of rapamycin complex 1) and is released in response to insulin. It has been suggested that this effect is due to 14-3-3 binding and leads to activation of mTORC1 signalling. In a similar manner to insulin, phorbol esters also activate mTORC1 signalling, in this case via PKC (protein kinase C) and ERK (extracellular-signal-regulated kinase). However, phorbol esters do not induce phosphorylation of PRAS40 at Thr (246), binding of 14-3-3 proteins to PRAS40 or its release from mTORC1. Mutation of Thr (246) to a serine residue permits phorbol esters to induce phosphorylation and binding to 14-3-3 proteins. Such phosphorylation is apparently mediated by RSKs (ribosomal S6 kinases), which lie downstream of ERK. However, although the PRAS40 (T246S) mutant binds to 14-3-3 better than wild-type PRAS40, each inhibits mTORC1 signalling to a similar extent. Our results show that activation of mTORC1 signalling by phorbol esters does not require PRAS40 to be phosphorylated at Thr (246), bind to 14-3-3 or be released from mTORC1. It is conceivable that phorbol esters activate mTORC1 by a distinct mechanism not involving PRAS40. Indeed, our results suggest that PRAS40 may not actually be involved in controlling mTORC1, but rather be a downstream target of mTORC1 that is regulated in response only to specific stimuli, such as insulin.

PMID: 21107834
Rapamycin increases the yield and effector function of human ?d T cells stimulated in vitro.
... or Erk in turn reduced the ... of mTOR.   (details)

EPHB2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 21107834

Rapamycin increases the yield and effector function of human ?d T cells stimulated in vitro.
Source

Cancer immunology, immunotherapy : CII (March 2011)

Abstract

Rapamycin increases the yield and effector function of human ?d T cells stimulated in vitro. Clinical strategies to exploit V?2Vd2 T cell responses for immunotherapy are confronted with short-term increases in cell levels or activity and the development of anergy that reduces the response to therapy with succeeding treatments. We are exploring strategies to increase the yield and durability of elicited V?2Vd2 T cell responses. One approach focuses on the mammalian target of rapamycin (mTOR), which is important for regulating T cell metabolism and function. In V?2Vd2 T cells, mTOR phosphorylates the S6K1 and eIF4EBP1 signaling intermediates after antigen stimulation. Rapamycin inhibited these phosphorylation events without impacting Akt or Erk activation, even though specific inhibition of Akt or Erk in turn reduced the activation of mTOR. The effects of rapamycin on the T cell receptor signaling pathway lead to increased proliferation of treated and antigen-exposed V?2Vd2 cells. Rapamycin altered the phenotype of antigen-specific V?2Vd2 cells by inducing a population shift from CD62L + CD69- to CD62L-CD69+, higher expression of CD25 or Bcl-2, lower levels of CCR5 and increased resistance to Fas-mediated cellular apoptosis. These changes were consistent with rapamycin promoting cell activation while decreasing the susceptibility to cell death that might occur by CCR5 or Fas signaling. Rapamycin treatment during antigen-stimulation of V?2Vd2 T cells may be a strategy for overcoming current obstacles in tumor immunotherapy.

PMID: 21289294
ERK and Akt signaling pathways function through parallel mechanisms to promote mTORC1 signaling.
... and ERK promote mTORC1 signaling ...   (details)

EPHB2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  mTORC1   (MLST8   RPTOR   MTOR )

PMID: 21289294

ERK and Akt signaling pathways function through parallel mechanisms to promote mTORC1 signaling.
Source

American journal of physiology. Cell physiology (May 2011)

Abstract

ERK and Akt signaling pathways function through parallel mechanisms to promote mTORC1 signaling. The mammalian target of rapamycin (mTOR) is a protein kinase that, when present in a complex referred to as mTOR complex 1 (mTORC1), acts as an important regulator of growth and metabolism. The activity of the complex is regulated through multiple upstream signaling pathways, including those involving Akt and the extracellular-regulated kinase (ERK). Previous studies have shown that, in part, Akt and ERK promote mTORC1 signaling through phosphorylation of a GTPase activator protein (GAP), referred to as tuberous sclerosis complex 2 (TSC2), that acts as an upstream inhibitor of mTORC1. In the present study we extend the earlier studies to show that activation of the Akt and ERK pathways acts in a synergistic manner to promote mTORC1 signaling. Moreover, we provide evidence that the Akt and ERK signaling pathways converge on TSC2, and that Akt phosphorylates residues on TSC2 distinct from those phosphorylated by ERK. The results also suggest that leucine-induced stimulation of mTORC1 signaling occurs through a mechanism distinct from TSC2 and the Akt and ERK signaling pathways. Overall, the results are consistent with a model in which Akt and ERK phosphorylate distinct sites on TSC2, leading to greater repression of its GAP activity, and consequently a magnified stimulation of mTORC1 signaling, when compared with either input alone. The results further suggest that leucine acts through a mechanism distinct from TSC2 to stimulate mTORC1 signaling.

PMID: 21659537
Pharmacological and genetic evaluation of proposed roles of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), and p90(RSK) in the control of mTORC1 protein signaling by phorbol esters.
... the requirements for MEK/ERK in ... of mTORC1 between ...   (details)

EPHB2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  mTORC1   (MLST8   RPTOR   MTOR )

PMID: 21659537

Pharmacological and genetic evaluation of proposed roles of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), and p90(RSK) in the control of mTORC1 protein signaling by phorbol esters.
Source

The Journal of biological chemistry (8/5/2011)

Abstract

Pharmacological and genetic evaluation of proposed roles of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), and p90 (RSK) in the control of mTORC1 protein signaling by phorbol esters. The mammalian target of rapamycin complex 1 (mTORC1) links the control of mRNA translation, cell growth, and metabolism to diverse stimuli. Inappropriate activation of mTORC1 can lead to cancer. Phorbol esters are naturally occurring products that act as potent tumor promoters. They activate isoforms of protein kinase C (PKCs) and stimulate the oncogenic MEK/ERK signaling cascade. They also activate mTORC1 signaling. Previous work indicated that mTORC1 activation by the phorbol ester PMA (phorbol 12-myristate 13-acetate) depends upon PKCs and may involve MEK. However, the precise mechanism (s) through which they activate mTORC1 remains unclear. Recent studies have implicated both the ERKs and the ERK-activated 90-kDa ribosomal S6 kinases (p90 (RSK)) in activating mTORC1 signaling via phosphorylation of TSC2 (a regulator of mTORC1) and/or the mTORC1 component raptor. However, the relative importance of each of these kinases and phosphorylation events for the activation of mTORC1 signaling is unknown. The recent availability of MEK (PD184352) and p90 (RSK) (BI-D1870) inhibitors of improved specificity allowed us to address the roles of these protein kinases in controlling mTORC1 in a variety of human and rodent cell types. In parallel, we used specific shRNAs against p90 (RSK1) and p90 (RSK2) to further test their roles in regulating mTORC1 signaling. Our data indicate that p90 (RSKs) are dispensable for the activation of mTORC1 signaling by phorbol esters in all cell types tested. Our data also reveal striking diversity in the requirements for MEK/ERK in the control of mTORC1 between different cell types, pointing to additional signaling connections between phorbol esters and mTORC1, which do not involve MEK/ERK. This study provides important information for the design of efficient strategies to combat the hyperactivation of mTORC1 signaling by oncogenic pathways.

PMID: 23291002
ERK1/2-dependent activation of mTOR/mTORC1/p70S6K regulates thrombin-induced RPE cell proliferation.
ERK1/2-dependent activation of mTOR/mTORC1/p70S6K regulates ...   (details)

EPHB2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  mTORC1   (MLST8   AKT1S1   RPTOR   MTOR )

PMID: 23291002

ERK1/2-dependent activation of mTOR/mTORC1/p70S6K regulates thrombin-induced RPE cell proliferation.
Source

Cellular signalling (April 2013)

Abstract

ERK1/2-dependent activation of mTOR/mTORC1/p70S6K regulates thrombin-induced RPE cell proliferation. Epithelial-mesenchymal transition (EMT), proliferation and migration of RPE cells characterize the development of proliferative vitreoretinopathy (PVR) and other fibro-proliferative eye diseases leading to blindness. A common event in these pathologies is the alteration of the BRB which allows the interaction of RPE cells with thrombin, a pro-inflammatory protease contained in serum. Thrombin promotion of cytoskeletal reorganization, proliferation, and migration has been reported in different cell types, although the molecular mechanisms involved in these processes remain poorly understood. Our previous work demonstrated that thrombin promotes RPE cell proliferation, cytoskeletal remodeling and migration, hallmark processes in the development of PVR. Thrombin induction of RPE cell proliferation requires PI3K, PDK1, and Akt/PKB (Akt) signaling leading to cyclin D1 gene expression. Since Akt functions as an upstream activator of mechanistic target of rapamycin complex 1 (mTORC1) and is also a downstream target for mTORC2, the aim of this work was to determine whether mTOR is involved in thrombin-induced RPE cell proliferation by regulating cyclin D1 expression in immortalized rat RPE-J cell line. Results demonstrate that thrombin-induced cyclin D1 expression and cell proliferation require Akt-independent phosphorylation/activation of mTOR at Ser 2448 mediated by PI3K/PKC-?/ERK1/2 signaling, concomitant to Akt-dependent activation of p70S6K carried by mTORC1.

PMID: 23422279
Estradiol-induced object recognition memory consolidation is dependent on activation of mTOR signaling in the dorsal hippocampus.
... -induced mTOR activation is dependent on ... of ERK and ...   (details)

EPHB2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 23422279

Estradiol-induced object recognition memory consolidation is dependent on activation of mTOR signaling in the dorsal hippocampus.
Source

Learning & memory (Cold Spring Harbor, N.Y.; 2013)

Abstract

Estradiol-induced object recognition memory consolidation is dependent on activation of mTOR signaling in the dorsal hippocampus. The mammalian target of rapamycin (mTOR) signaling pathway is an important regulator of protein synthesis and is essential for various forms of hippocampal memory. Here, we asked whether the enhancement of object recognition memory consolidation produced by dorsal hippocampal infusion of 17ß-estradiol (E (2)) is dependent on mTOR signaling in the dorsal hippocampus, and whether E (2) -induced mTOR signaling is dependent on dorsal hippocampal phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) activation. We first demonstrated that the enhancement of object recognition induced by E (2) was blocked by dorsal hippocampal inhibition of ERK, PI3K, or mTOR activation. We then showed that an increase in dorsal hippocampal ERK phosphorylation 5 min after intracerebroventricular (ICV) E (2) infusion was also blocked by dorsal hippocampal infusion of the three cell signaling inhibitors. Next, we found that ICV infusion of E (2) increased phosphorylation of the downstream mTOR targets S6K (Thr-421) and 4E-BP1 in the dorsal hippocampus 5 min after infusion, and that this phosphorylation was blocked by dorsal hippocampal infusion of inhibitors of ERK, PI3K, and mTOR. Collectively, these data demonstrate for the first time that activation of the dorsal hippocampal mTOR signaling pathway is necessary for E (2) to enhance object recognition memory consolidation and that E (2) -induced mTOR activation is dependent on upstream activation of ERK and PI3K signaling.

PMID: 23431403
Kinase suppressor of ras 1 is not required for the generation of regulatory and memory T cells.
... of ERK following ... is required for sustained mTOR complex 1 (mTORC1) activation ...   (details)

EPHB2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 23431403

Kinase suppressor of ras 1 is not required for the generation of regulatory and memory T cells.
Source

PloS one (2013)

Abstract

Kinase suppressor of ras 1 is not required for the generation of regulatory and memory T cells. The mammalian target of rapamycin (mTOR) kinase is a critical regulator of the differentiation of helper and regulatory CD4+ T cells, as well as memory CD8+ T cells. In this study, we investigated the role of the ERK signaling pathway in regulating mTOR activation in T cells. We showed that activation of ERK following TCR engagement is required for sustained mTOR complex 1 (mTORC1) activation. Absence of kinase suppressor of Ras 1 (KSR1), a scaffold protein of the ERK signaling pathway, or inhibition of ERK resulted in decreased mTORC1 activity following T cell activation. However, KSR1-deficient mice displayed normal regulatory CD4+ T cell development, as well as normal memory CD8+ T cell responses to LCMV and Listeria monocytogenes infection. These data indicate that despite its role in mTORC1 activation, KSR1 is not required in vivo for mTOR-dependent T cell differentiation.

... of ERK resulted in decreased mTORC1 activity ...   (details)

EPHB2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  mTORC1   (MLST8   RPTOR   MTOR )

PMID: 23431403

Kinase suppressor of ras 1 is not required for the generation of regulatory and memory T cells.
Source

PloS one (2013)

Abstract

Kinase suppressor of ras 1 is not required for the generation of regulatory and memory T cells. The mammalian target of rapamycin (mTOR) kinase is a critical regulator of the differentiation of helper and regulatory CD4+ T cells, as well as memory CD8+ T cells. In this study, we investigated the role of the ERK signaling pathway in regulating mTOR activation in T cells. We showed that activation of ERK following TCR engagement is required for sustained mTOR complex 1 (mTORC1) activation. Absence of kinase suppressor of Ras 1 (KSR1), a scaffold protein of the ERK signaling pathway, or inhibition of ERK resulted in decreased mTORC1 activity following T cell activation. However, KSR1-deficient mice displayed normal regulatory CD4+ T cell development, as well as normal memory CD8+ T cell responses to LCMV and Listeria monocytogenes infection. These data indicate that despite its role in mTORC1 activation, KSR1 is not required in vivo for mTOR-dependent T cell differentiation.