Oncogenic met receptor induces cell-cycle progression inXenopus oocytes independent of direct Grb2 and Shc binding or mos synthesis, but requires phosphatidylinositol 3-kinase and raf signaling

2006 ◽  
Vol 207 (1) ◽  
pp. 271-285 ◽  
Author(s):  
Kathleen Mood ◽  
Caroline Saucier ◽  
Akihiko Ishimura ◽  
Yong-Sik Bong ◽  
Hyun-Shik Lee ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Phosphatidylinositol 3 Kinase ◽  
Met Receptor ◽  
Cycle Progression ◽  
Phosphatidylinositol 3

scholarly journals p70s6k Integrates Phosphatidylinositol 3-Kinase and Rapamycin-Regulated Signals for E2F Regulation in T Lymphocytes

1999 ◽  
Vol 19 (7) ◽  
pp. 4729-4738 ◽  
Author(s):  
Paul Brennan ◽  
J. W. Babbage ◽  
G. Thomas ◽  
Doreen Cantrell
Keyword(s):  
Cell Cycle ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Cycle Progression ◽  
Transcriptional Activity ◽  
Interleukin 2 ◽  
Cell Cycle Checkpoint ◽  
Phosphatidylinositol 3 Kinase ◽  
Cycle Progression ◽  
Phosphatidylinositol 3

ABSTRACT In T lymphocytes, the hematopoietic cytokine interleukin-2 (IL-2) uses phosphatidylinositol 3-kinase (PI 3-kinase)-induced signaling pathways to regulate E2F transcriptional activity, a critical cell cycle checkpoint. PI 3-kinase also regulates the activity of p70s6k, the 40S ribosomal protein S6 kinase, a response that is abrogated by the macrolide rapamycin. This immunosuppressive drug is known to prevent T-cell proliferation, but the precise point at which rapamycin regulates T-cell cycle progression has yet to be elucidated. Moreover, the effects of rapamycin on, and the role of p70s6k in, IL-2 and PI 3-kinase activation of E2Fs have not been characterized. Our present results show that IL-2- and PI 3-kinase-induced pathways for the regulation of E2F transcriptional activity include both rapamycin-resistant and rapamycin-sensitive components. Expression of a rapamycin-resistant mutant of p70s6k in T cells could restore rapamycin-suppressed E2F responses. Thus, the rapamycin-controlled processes involved in E2F regulation appear to be mediated by p70s6k. However, the rapamycin-resistant p70s6k could not rescue rapamycin inhibition of T-cell cycle entry, consistent with the involvement of additional, rapamycin-sensitive pathways in the control of T-cell cycle progression. The present results thus show that p70s6k is able to regulate E2F transcriptional activity and provide direct evidence for the first time for a link between IL-2 receptors, PI 3-kinase, and p70s6k that regulates a crucial G1 checkpoint in T lymphocytes.

Changes in phosphatidylinositol 3-kinase 55 kDa gamma expression and subcellular localization may be caspase 6 dependent in paraquat-induced SH-SY5Y apoptosis

2013 ◽  
Vol 33 (7) ◽  
pp. 761-771 ◽  
Author(s):  
Y Zhou ◽  
F Li ◽  
X Tian ◽  
B Wang ◽  
M Ding ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Subcellular Localization ◽  
Cell Cycle Progression ◽  
Pathological Feature ◽  
Phosphatidylinositol 3 Kinase ◽  
Cycle Progression ◽  
Expression Levels ◽  
Caspase 6 ◽  
Induced Apoptosis ◽  
Phosphatidylinositol 3

The neurotoxin paraquat (PQ) causes apoptosis of dopaminergic neurons in mammalian cell culture and animal models, mimicking an important pathological feature of Parkinson’s disease (PD). The phosphoinositide 3-kinase (PI3K)/Akt pathway is critical for several major survival signals in central nervous system neurons. Phosphatidylinositol 3-kinase 55 kDa gamma ( p55PIK) is a regulatory subunit of PI3Ks with important roles in cell proliferation, antiapoptosis, and cell cycle progression. However, p55PIK involvement in mechanisms regarding progression and maintenance of neurodegenerative diseases is largely undetermined. We used PQ-induced apoptosis in human dopaminergic SH-SY5Y cells to investigate the association between p55PIK expression levels, subcellular location, and apoptosis. p55PIK expression was reduced in SH-SY5Y cells and p55PIK messenger RNA and protein expression levels were decreased after PQ treatment. Apoptosis induced by PQ was associated with caspase activation and decreased p55PIK expression. Restoration of p55PIK expression was observed after coincubation with a caspase inhibitor. Overexpressed full-length p55PIK in SH-SY5Y and human embryonic kidney 293 cells showed specific distribution in the nucleus and was cleaved in vitro by recombinant caspase 6 (C6), but not C3 and C7. A p55PIK construct lacking 24 N-terminal amino acids (N24) was tested for the presence of a potential C6-recognizable sequence and was found to express its proteins outside the nucleus. The results suggest that p55PIK may be involved in PQ-induced apoptosis signal transduction and that N24 is crucial for p55PIK subcellular localization. Thus, p55PIK could be a substrate of activated C6 during apoptosis, leading to loss of original biological functions and redistribution to disturb cell cycle progression.

scholarly journals Studies of partially transforming polyomavirus mutants establish a role for phosphatidylinositol 3-kinase in activation of pp70 S6 kinase.

1996 ◽  
Vol 16 (6) ◽  
pp. 2728-2735 ◽  
Author(s):  
J Dahl ◽  
R Freund ◽  
J Blenis ◽  
T L Benjamin
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Soft Agar ◽  
Signalling Pathways ◽  
Wild Type ◽  
Phosphatidylinositol 3 Kinase ◽  
Cycle Progression ◽  
S6 Kinase ◽  
Ribosomal Protein S6 ◽  
Phosphatidylinositol 3

Infection of mouse fibroblasts by wild-type polyomavirus results in increased phosphorylation of ribosomal protein S6 (D.A. Talmage, J. Blenis, and T.L. Benjamin, Mol. Cell. Biol. 8:2309-2315, 1988). Here we identify pp70 S6 kinase (pp70S6K) as a target for signal transduction events leading from polyomavirus middle tumor antigen (mT). Two partially transforming virus mutants altered in different mT signalling pathways have been studied to elucidate the pathway leading to S6 phosphorylation. An upstream role for mT-phosphatidylinositol 3-kinase (PI3K) complexes in pp70S6K activation is implicated by the failure of 315YF, a mutant unable to promote PI3K binding, to elicit a response. This conclusion is supported by studies using wortmannin, a known inhibitor of PI3K. In contrast, stable interaction of mT with Shc, a protein thought to be involved upstream of Ras, is dispensable for pp70S6K activation. 250YS, a mutant mT which retains a binding site for PI3K but lacks one for Shc, stimulates pp70S6K to wild-type levels. Mutants 315YF and 250YS induce partial transformation of rats fibroblasts with distinct phenotypes, as judged from morphological and growth criteria. Neither mutant induces growth in soft agar, indicating that an increase in S6 phosphorylation, while necessary for cell cycle progression in normal mitogenesis, is not sufficient for anchorage-independent cell growth. In the polyomavirus systems, the latter requires integration of signals from mT involving both Shc and PI3K.

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