Signal Transduction Pathways Involved in Phosphorylation and Activation of p70S6K Following Exposure to UVA Irradiation

Zhang, Yiguo; Dong, Ziming; Nomura, Masatoshi; Zhong, Shuming; Chen, Nanyue; Bode, Ann M.; Dong, Zigang

doi:10.1074/jbc.m009047200

Cited by 90 publications

(98 citation statements)

References 70 publications

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“…The stimulating effect upon UV exposure on S6K activity is rapamycin sensitive (Parrott and Templeton, 1999;Brenneisen et al, 2000;Ding et al, 2002;Huang et al, 2002). Interestingly, additional pathways (p38, ERK1/2, JNK and PI3K) may also affect S6K phosphorylation (Zhang et al, 2001). The activating effect can be attributed to the generation of reactive oxygen (ROS) species that accumulate in response to UV exposure, whereas pretreatment with ROS scavengers or antioxidants prevents S6K activation .…”

Section: Ultraviolet and Rosmentioning

confidence: 99%

Stress and mTORture signaling

2006

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Section: Ultraviolet and Rosmentioning

confidence: 99%

Stress and mTORture signaling

2006

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“…The activity of p70S6 kinase was assayed by using an immune complex in vitro kinase assay by modification of the methods of Zhang et al (52). Briefly, confluent muscle cells were rendered quiescent by incubation in serum-free DMEM for 24 h. Cells were stimulated with IGF-I (100 nM) for the indicated periods of time (0-24 h) in the presence or absence of various inhibitors.…”

Section: Culture Of Isolated Smooth Muscle Cells From Normal Human Jementioning

confidence: 99%

IGF-I elicits growth of human intestinal smooth muscle cells by activation of PI3K, PDK-1, and p70S6 kinase

Kuemmerle

2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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Endogenous IGF-I regulates growth of human intestinal smooth muscle cells by jointly activating phosphatidylinositol 3-kinase (PI3K) and ERK1/2. The 70-kDa ribosomal S6 kinase (p70S6 kinase) is a key regulator of cell growth activated by several independently regulated kinases. The present study characterized the role of p70S6 kinase in IGF-I-induced growth of human intestinal smooth muscle cells and identified the mechanisms of p70S6 kinase activation. IGF-I-induced growth elicited via either the PI3K or ERK1/2 pathway required activation of p70S6 kinase. IGF-I elicited concentration-dependent activation of PI3K, 3-phosphoinositide-dependent kinase-1 (PDK-1), and p70S6 kinase that was sequential and followed similar time courses. IGF-I caused time-dependent and concentration-dependent phosphorylation of p70S6 kinase on Thr421/Ser424, Thr389, and Thr229 that paralleled p70S6 kinase activation. p70S6 kinase(Thr421/Ser424) phosphorylation was PI3K dependent and PDK-1 independent, whereas p70S6 kinase(Thr389) and p70S6 kinase(Thr229) phosphorylation and p70S6 kinase activation were PI3K dependent and PDK-1 dependent. IGF-I elicited sequential Akt(Ser308), Akt(Ser473), and mammalian target of rapamycin(Ser2448) phosphorylation; however, transfection of muscle cells with kinase-inactive Akt1(K179M) showed that these events were not required for IGF-I to activate p70S6 kinase and stimulate proliferation of human intestinal muscle cells.

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“…Kinases implicated in the phosphorylation and activation of p70 S6 kinase include mTOR (mammalian Target of Rapamycin) and PDK-1, which is responsible for phosphorylation of Thr229 (Dufner & Thomas, 1999). Recent studies have also indicated a role for p42/p44 MAPK, p38 MAPK and JNK in the phosphorylation and activation of p70 S6 kinase (Zhang et al, 2001). In addition, Zhang et al (2001) (Zhang et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have also indicated a role for p42/p44 MAPK, p38 MAPK and JNK in the phosphorylation and activation of p70 S6 kinase (Zhang et al, 2001). In addition, Zhang et al (2001) (Zhang et al, 2001). In this study, histamine-induced increases in p70 S6 kinase phosphorylation at Thr 421 /Ser 424 were completely blocked by PD 98059, wortmannin and LY 294002 but only partially sensitive to the mTOR inhibitor rapamycin.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that the rapamycin-sensitive phosphorylation sites located in the autoinhibitory domain (including Thr 421 / Ser 424 ) do not serve as a substrate for mTOR (Burnett et al, 1998;Dufner & Thomas, 1999). Hence, it has been suggested that inhibition of p70 S6 kinase phosphorylation at Thr 421 / Ser 424 by rapamycin may occur via rapamycin-induced protein phosphatase 2A activation (Zhang et al, 2001). These ®ndings may explain the sensitivity of histamine and EGF-induced p70 S6 kinase phosphorylation at Thr 421 /Ser 424 to rapamycin.…”

Section: Discussionmentioning

confidence: 99%

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Stimulation of protein kinase B and p70 S6 kinase by the histamine H₁ receptor in DDT₁MF‐2 smooth muscle cells

Dickenson

2002

British J Pharmacology

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1 Previous studies have shown that the histamine H 1 receptor activates p42/p44 mitogen-activated protein kinases (MAPK) in DDT 1 MF-2 smooth muscle cells via a phosphatidylinositol 3-kinase (PI-3K)-dependent pathway. In this study the e ect of histamine H 1 receptor stimulation on protein kinase B (PKB) and p70 S6 kinase, both of which are downstream targets of PI-3K, has been investigated. Increases in PKB and p70 S6 kinase activation were monitored by Western blotting using phospho-speci®c PKB (Ser 473 ) and p70 S6 kinase (Thr 421 /Ser 424 ) antibodies. 2 Histamine stimulated time and concentration-dependent increases in the phosphorylation of PKB and p70 S6 kinase in DDT 1 MF-2 cells. Both responses were completely inhibited by the histamine H 1 receptor antagonist mepyramine and following pre-treatment with pertussis toxin, to block G i /G o protein dependent pathways. 3 The PI-3K inhibitors wortmannin (IC 50 5.9+0.5 nM) and LY 294002 (IC 50 6.9+0.8 mM) attenuated the increase in PKB phosphorylation induced by histamine (100 mM) in a concentration-dependent manner. 4 Histamine-induced increases in p70 S6 kinase phosphorylation were partially sensitive to rapamycin (20 nM; 68% inhibition) but completely blocked by wortmannin (100 nM), LY 294002 (30 mM) and the MAPK kinase inhibitor PD 98059 (50 mM). 5 In summary, these data demonstrate that the histamine H 1 receptor stimulates PKB and p70 S6 kinase phosphorylation in DDT 1 MF-2 smooth muscle cells. However, functional studies revealed that histamine does not stimulate DDT 1 MF-2 cell proliferation or attenuate staurosporine-induced caspase-3 activity. The challenge for future research will be to link the stimulation of these kinase pathways with the physiological and pathophysiological roles of the histamine H 1 receptor.

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Signal Transduction Pathways Involved in Phosphorylation and Activation of p70S6K Following Exposure to UVA Irradiation

Cited by 90 publications

References 70 publications

Stress and mTORture signaling

Stress and mTORture signaling

IGF-I elicits growth of human intestinal smooth muscle cells by activation of PI3K, PDK-1, and p70S6 kinase

Stimulation of protein kinase B and p70 S6 kinase by the histamine H₁ receptor in DDT₁MF‐2 smooth muscle cells

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Signal Transduction Pathways Involved in Phosphorylation and Activation of p70S6K Following Exposure to UVA Irradiation

Cited by 90 publications

References 70 publications

Stress and mTORture signaling

Stress and mTORture signaling

IGF-I elicits growth of human intestinal smooth muscle cells by activation of PI3K, PDK-1, and p70S6 kinase

Stimulation of protein kinase B and p70 S6 kinase by the histamine H1 receptor in DDT1MF‐2 smooth muscle cells

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Product

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Stimulation of protein kinase B and p70 S6 kinase by the histamine H₁ receptor in DDT₁MF‐2 smooth muscle cells