Involvement of intact inositol‐1,4,5‐trisphosphate‐sensitive Ca<sup>2+</sup> stores in cell cycle progression at the G1/S boundary in serum‐stimulated human fibroblasts

Takuwa, Noriko; Zhou, Wei; Kumada, Mamoru; Takuwa, Yoh

doi:10.1016/0014-5793(95)00080-s

Cited by 24 publications

(22 citation statements)

References 29 publications

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“…6A). By contrast, p27 kip1 was effectively downregulated in cells that were growth arrested by the additions of the active calmodulin antagonist W-7 (50-52), the endoplasmic reticulum Ca 2ϩ pump blocker thapsigargin (49), and phorbol-12, 13-dibutyrate (61, 62) late in the G 1 phase (Fig. 6B).…”

Section: Resultsmentioning

confidence: 99%

Ras Activity Late in G₁ Phase Required for p27^kip1 Downregulation, Passage through the Restriction Point, and Entry into S Phase in Growth Factor-Stimulated NIH 3T3 Fibroblasts

Takuwa

1997

Molecular and Cellular Biology

169

155

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It is well documented that Ras functions as a molecular switch for reentry into the cell cycle at the border between G 0 and G 1 by transducing extracellular growth stimuli into early G 1 mitogenic signals. In the present study, we investigated the role of Ras during the late stage of the G 1 phase by using NIH 3T3 (M17) fibroblasts in which the expression of a dominant negative Ras mutant, p21Ha-Ras(Asn17) , is induced in response to dexamethasone treatment. We found that delaying the expression of Ras(Asn17) until late in the G 1 phase by introducing dexamethasone 3 h after the addition of epidermal growth factor (EGF) abolished the downregulation of the p27 kip1 cyclin-dependent kinase (CDK) inhibitor which normally occurred during this period, with resultant suppression of cyclin Ds/CDK4 and cyclin E/CDK2 and G 1 arrest. The immunodepletion of p27 When serum-deprived quiescent cells are exposed to mitogenic stimuli, including growth factors, G protein-coupled receptor agonists, and hemopoietic cytokines, cellular Ras activates within a few minutes (12,44,45,54). Active Ras then interacts with and activates a number of downstream effectors, including Raf family kinases and p110 catalytic subunits of phosphatidylinositol-3-kinase (43,55,60). The serine and threonine protein kinase cascade consisting of Raf, MEK, and mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinase [ERK]) is one of the best-characterized Ras effector systems (9). Accumulated evidence indicates that ERKs participate in the transcriptional activation of certain immediate early genes by directly phosphorylating p62 TCF / Elk-1 (13, 21), an Ets family transcription factor involved in ternary complex formation at the serum response element (19). It has also been reported recently (57) that ERKs mediate gene expression through the phosphorylation and activation of p90 RSK2 , which phosphorylates CREB to activate its transactivation potential. These findings provide compelling evidence that Ras acts as a molecular switch for reentry into the cell cycle at the border between G 0 and G 1 by transducing extracellular stimuli into a number of early G 1 mitogenic signals.By contrast, the role of Ras in later phases of the cell cycle is poorly understood. The ratio of GTP-GDP bound to Ras promptly rises after the addition of growth factors and then declines over a period of hours to a steady-state level that is slightly higher than or very close to the basal unstimulated value (31). Stacey and coworkers (11, 30) previously demonstrated that the microinjection of a neutralizing anti-Ras antibody into NIH 3T3 fibroblasts potently inhibited the initiation of DNA synthesis whether the microinjection was performed before serum stimulation or 6 h afterward. These researchers also showed that the anti-Ras antibody introduced into cells after entry into the S phase was much less inhibitory for the ongoing DNA synthesis (30). These results support the notion that the function of Ras is required for passage through the restriction (R) po...

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Section: Resultsmentioning

confidence: 99%

Ras Activity Late in G₁ Phase Required for p27^kip1 Downregulation, Passage through the Restriction Point, and Entry into S Phase in Growth Factor-Stimulated NIH 3T3 Fibroblasts

Takuwa

1997

Molecular and Cellular Biology

169

155

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“…13 In mammalian cells, an anti-IP3R1 antibody blocked IICR and cell cycle after fertilization. 14 Thapsigargininduced depletion of IP3-sensitive Ca 2ϩ stores completely inhibited cyclin-A expression, cdk2 activation, DNA synthesis, and G 1 /S transitions in human fibroblasts, 15 and proliferation was reduced in mouse fibroblasts stably expressing truncated IP3R1 mutants. 16 IP3R1 knockdown in T cells blocked [Ca 2ϩ ] i elevation as well as interleukin (IL)-2 induction, implicating IP3R1 in T cell proliferation.…”

mentioning

confidence: 99%

c-Myb–Dependent Inositol 1,4,5-Trisphosphate Receptor Type-1 Expression in Vascular Smooth Muscle Cells

Afroze

Sadi²,

Momen³

et al. 2007

ATVB

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“…Nicotine self-administration impairs the ability of T cells to mobilize ionized Ca 2ϩ , which is critical for the progression of T cells from the G 0 /G 1 to the S phase of the cell cycle (Clapham, 1995;Takuwa et al, 1995). Defects in T cell signaling in response to Con A are also observed in T cells from human cigarette smokers (Suzuki et al, 1999) and rats given chronic cigarette smoke .…”

Section: Discussionmentioning

confidence: 99%

Chronic Self-Administration of Nicotine in Rats Impairs T Cell Responsiveness

Kalra¹,

Singh²,

Kracko³

et al. 2002

J Pharmacol Exp Ther

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Chronic exposure of rodents to nicotine via subcutaneously or intracerebroventricularly implanted miniosmotic pumps affects T cell function. However, this method of continuous nicotine administration does not replicate the self-motivated administration of nicotine in human smokers. To determine whether nicotine impairs the immune system under conditions pertinent to human smokers, we investigated the T cell responsiveness of male Lewis rats self-administering (SA) nicotine (0.03 mg/kg of body weight per injection) 40 to 50 times/day for 5 weeks, using a model of virtually unlimited access to nicotine. Compared with sham control animals, the concanavalin A-induced proliferation of spleen cells from SA rats was significantly decreased. Moreover, the ability of spleen cells to mobilize intracellular Ca 2ϩ after ligation of the T cell antigen receptor (TCR) with an anti-␣␤ TCR antibody was significantly less in SA than in control rats. In addition, inositol 1,4,5-trisphosphate (IP 3 )-sensitive intracellular Ca 2ϩ stores were markedly depleted in spleen cells from SA animals. These results suggest that chronic nicotine self-administration suppresses T cell responsiveness, and this suppression may result from an impaired TCR-mediated signaling that stems from the depletion of IP 3 -sensitive intracellular Ca 2ϩ stores.Cigarette smoking is a major health risk factor and significantly increases the incidence of several diseases (reviewed in Sopori et al., 1994). It is hypothesized that this increased disease susceptibility reflects cigarette smoke-induced changes in the immune system (Holt and Keast, 1977). Chronic exposure to cigarette smoke suppresses a wide range of immunological parameters in human and animal models , and this immunosuppression is associated with the particulate phase of cigarette smoke (Sopori et al., 1993). Nicotine is the major neuroactive chemical in cigarette smoke, and previous data from this and other laboratories suggest that nicotine suppresses immune and inflammatory responses (reviewed in Sopori, 1998). Chronic s.c. or i.c.v. exposure of rats to nicotine affects T cell mitogenesis and the ability of T cells to migrate from the G 0 /G 1 into the S phase of the cell cycle (Geng et al., 1996;. Ligation of the T cell antigen receptor (TCR) by anti-TCR antibodies is an in vitro model for an antigeninduced T cell activation that stimulates protein tyrosine kinases, leading to activation of phospholipase C-␥1, production of inositol 1,4,5-trisphosphate (IP 3 ) (Nishibe et al., 1990;Robey and Allison, 1995), and the mobilization of intracellular Ca 2ϩ due to IP 3 . Effects of nicotine on T cell proliferation are associated with impaired TCR-mediated signaling in T cells, including inhibition of the ability to raise intracellular concentration of ionized Ca 2ϩ ([Ca 2ϩ ] i ) (Geng et al., 1995(Geng et al., , 1996. Chronic round-the-clock exposure of rats to nicotine via miniosmotic pumps inhibits the [Ca 2ϩ ] i response in T cells (Geng et al., 1996); however, it is difficult to assume...

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Involvement of intact inositol‐1,4,5‐trisphosphate‐sensitive Ca²⁺ stores in cell cycle progression at the G1/S boundary in serum‐stimulated human fibroblasts

Cited by 24 publications

References 29 publications

Ras Activity Late in G₁ Phase Required for p27^kip1 Downregulation, Passage through the Restriction Point, and Entry into S Phase in Growth Factor-Stimulated NIH 3T3 Fibroblasts

Ras Activity Late in G₁ Phase Required for p27^kip1 Downregulation, Passage through the Restriction Point, and Entry into S Phase in Growth Factor-Stimulated NIH 3T3 Fibroblasts

c-Myb–Dependent Inositol 1,4,5-Trisphosphate Receptor Type-1 Expression in Vascular Smooth Muscle Cells

Chronic Self-Administration of Nicotine in Rats Impairs T Cell Responsiveness

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Involvement of intact inositol‐1,4,5‐trisphosphate‐sensitive Ca2+ stores in cell cycle progression at the G1/S boundary in serum‐stimulated human fibroblasts

Cited by 24 publications

References 29 publications

Ras Activity Late in G1 Phase Required for p27kip1 Downregulation, Passage through the Restriction Point, and Entry into S Phase in Growth Factor-Stimulated NIH 3T3 Fibroblasts

Ras Activity Late in G1 Phase Required for p27kip1 Downregulation, Passage through the Restriction Point, and Entry into S Phase in Growth Factor-Stimulated NIH 3T3 Fibroblasts

c-Myb–Dependent Inositol 1,4,5-Trisphosphate Receptor Type-1 Expression in Vascular Smooth Muscle Cells

Chronic Self-Administration of Nicotine in Rats Impairs T Cell Responsiveness

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Involvement of intact inositol‐1,4,5‐trisphosphate‐sensitive Ca²⁺ stores in cell cycle progression at the G1/S boundary in serum‐stimulated human fibroblasts

Ras Activity Late in G₁ Phase Required for p27^kip1 Downregulation, Passage through the Restriction Point, and Entry into S Phase in Growth Factor-Stimulated NIH 3T3 Fibroblasts

Ras Activity Late in G₁ Phase Required for p27^kip1 Downregulation, Passage through the Restriction Point, and Entry into S Phase in Growth Factor-Stimulated NIH 3T3 Fibroblasts