scholarly journals Dual Stimulation of Ras/Mitogen-Activated Protein Kinase and Rhoa by Cell Adhesion to Fibronectin Supports Growth Factor–Stimulated Cell Cycle Progression

2000 ◽  
Vol 151 (7) ◽  
pp. 1413-1422 ◽  
Author(s):  
Erik H.J. Danen ◽  
Petra Sonneveld ◽  
Arnoud Sonnenberg ◽  
Kenneth M. Yamada
Keyword(s):  
Cell Cycle ◽  
Growth Factors ◽  
Growth Factor ◽  
Protein Kinase ◽  
Cell Cycle Progression ◽  
Mitogen Activated Protein Kinase ◽  
Cycle Progression ◽  
Extracellular Matrix Components ◽  
Mitogen Activated Protein ◽  
Stimulation Of

In cellular transformation, activated forms of the small GTPases Ras and RhoA can cooperate to drive cells through the G1 phase of the cell cycle. Here, we show that a similar but substrate-regulated mechanism is involved in the anchorage-dependent proliferation of untransformed NIH-3T3 cells. Among several extracellular matrix components tested, only fibronectin supported growth factor–induced, E2F-dependent S phase entry. Although all substrates supported the mitogen-activated protein kinase (MAPK) response to growth factors, RhoA activity was specifically enhanced on fibronectin. Moreover, induction of cyclin D1 and suppression of p21Cip/Waf occurred specifically, in a Rho-dependent fashion, in cells attached to fibronectin. This ability of fibronectin to stimulate both Ras/MAPK- and RhoA-dependent signaling can explain its potent cooperation with growth factors in the stimulation of cell cycle progression.

scholarly journals Regulation of cyclin D1 expression and cell cycle progression by mitogen-activated protein kinase cascade

1999 ◽  
Vol 56 (4) ◽  
pp. 1258-1261 ◽  
Author(s):  
Yoshio Terada ◽  
Seiji Inoshita ◽  
Osamu Nakashima ◽  
Michio Kuwahara ◽  
Sei Sasaki ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Mitogen Activated Protein Kinase ◽  
Cycle Progression ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Protein Kinase Cascade

scholarly journals Cell Cycle Arrest and Reversion of Ras-Induced Transformation by a Conditionally Activated Form of Mitogen-Activated Protein Kinase Kinase Kinase 3

1999 ◽  
Vol 19 (5) ◽  
pp. 3857-3868 ◽  
Author(s):  
Heidrun Ellinger-Ziegelbauer ◽  
Kathleen Kelly ◽  
Ulrich Siebenlist
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Cyclin D1 ◽  
Stress Responses ◽  
Cell Cycle Progression ◽  
Cellular Transformation ◽  
Mitogen Activated Protein Kinase ◽  
Cycle Progression ◽  
Mapk Kinase ◽  
Mitogen Activated Protein

ABSTRACT Signal-induced proliferation, differentiation, or stress responses of cells depend on mitogen-activated protein kinase (MAPK) cascades, the core modules of which consist of members of three successively acting kinase families (MAPK kinase kinase [MAP3K], MAPK kinase, and MAPK). It is demonstrated here that the MEKK3 kinase inhibits cell proliferation, a biologic response not commonly associated with members of the MAP3K family of kinases. A conditionally activated form of MEKK3 stably expressed in fibroblasts arrests these cells in early G1. MEKK3 critically blocks mitogen-driven expression of cyclin D1, a cyclin which is essential for progression of fibroblasts through G1. The MEKK3-induced block of cyclin D1 expression and of cell cycle progression may be mediated via p38 MAPK, a downstream effector of MEKK3. The MEKK3-mediated block of proliferation also reverses Ras-induced cellular transformation, suggesting possible tumor-suppressing functions for this kinase. Together, these results suggest an involvement of the MEKK3 kinase in negative regulation of cell cycle progression, and they provide the first insights into biologic activities of this kinase.

scholarly journals Disruption of the Rb-Raf-1 Interaction Inhibits Tumor Growth and Angiogenesis

2004 ◽  
Vol 24 (21) ◽  
pp. 9527-9541 ◽  
Author(s):  
Piyali Dasgupta ◽  
Jiazhi Sun ◽  
Sheng Wang ◽  
Gina Fusaro ◽  
Vicki Betts ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Mitogen Activated Protein Kinase ◽  
Tubule Formation ◽  
Cycle Progression ◽  
Cyclin Dependent Kinases ◽  
Quiescent Cells ◽  
Stimulation Of

ABSTRACT The retinoblastoma tumor suppressor protein (Rb) plays a vital role in regulating mammalian cell cycle progression and inactivation of Rb is necessary for entry into S phase. Rb is inactivated by phosphorylation upon growth factor stimulation of quiescent cells, facilitating the transition from G1 phase to S phase. Although the signaling events after growth factor stimulation have been well characterized, it is not yet clear how these signals contact the cell cycle machinery. We had found previously that growth factor stimulation of quiescent cells lead to the direct binding of Raf-1 kinase to Rb, leading to its inactivation. Here we show that the Rb-Raf-1 interaction occurs prior to the activation of cyclin and/or cyclin-dependent kinases and facilitates normal cell cycle progression. Raf-1-mediated inactivation of Rb is independent of the mitogen-activated protein kinase cascade, as well as cyclin-dependent kinases. Binding of Raf-1 seemed to correlate with the dissociation of the chromatin remodeling protein Brg1 from Rb. Disruption of the Rb-Raf-1 interaction by a nine-amino-acid peptide inhibits Rb phosphorylation, cell proliferation, and vascular endothelial growth factor-mediated capillary tubule formation. Delivery of this peptide by a carrier molecule led to a 79% reduction in tumor volume and a 57% reduction in microvessel formation in nude mice. It appears that Raf-1 links mitogenic signaling to Rb and that disruption of this interaction could aid in controlling proliferative disorders.

Sperm penetration of immature and maturing oocytes does not affect phosphorylation of mitogen-activated protein kinase in pigs

2003 ◽  
Vol 15 (7) ◽  
pp. 383 ◽  
Author(s):  
H. M. Quan ◽  
X. Q. Meng ◽  
Y. Hou ◽  
Q. Y. Sun
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Cell Cycle Progression ◽  
Germinal Vesicle ◽  
Mitogen Activated Protein Kinase ◽  
Cycle Progression ◽  
Mapk Phosphorylation ◽  
Mitogen Activated Protein ◽  
Sperm Penetration

Pig oocytes cultured in vitro for 0, 25, 33 and 44 h were inseminated by frozen–thawed ejaculated sperm. At specified times after insemination, sperm penetration, cell cycle progression and mitogen-activated protein kinase (MAPK) phosphorylation were evaluated. It was shown that: (1) oocytes at various maturational stages could be penetrated by sperm; (2) sperm penetration did not affect meiotic cell cycle progression; (3) sperm penetration of germinal vesicle (GV) oocytes and maturing oocytes did not alter MAPK phosphorylation; and (4) when premetaphase I (pre-MI) and metaphase I (MI) oocytes, in which MAPK was activated, were fertilised, no evident MAPK dephosphorylation was detected as in metaphase II oocytes. The data suggest that sperm penetration before oocyte maturation does not affect MAPK phosphorylation and that the machinery inactivating MAPK upon fertilisation is not developed in maturing (pre-MI to MI) oocytes.

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