scholarly journals Mediation of Basic Fibroblast Growth Factor-Induced Lactotropic Cell Proliferation by Src-Ras-Mitogen-Activated Protein Kinase p44/42 Signaling

Endocrinology ◽  
2005 ◽  
Vol 146 (4) ◽  
pp. 1948-1955 ◽  
Author(s):  
Kirti Chaturvedi ◽  
Dipak K. Sarkar
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Protein Kinase ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Fibroblast Growth ◽  
Mitogen Activated Protein

scholarly journals Oncogenic K-Ras and Basic Fibroblast Growth Factor Prevent FAS-Mediated Apoptosis in Fibroblasts through Activation of Mitogen-Activated Protein Kinase

2000 ◽  
Vol 148 (3) ◽  
pp. 557-566 ◽  
Author(s):  
Hirotaka Kazama ◽  
Shin Yonehara
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Active Form ◽  
Mitogen Activated Protein Kinase ◽  
Expression Cloning ◽  
Fibroblast Growth ◽  
Mitogen Activated Protein ◽  
Constitutively Active

By an expression cloning method using Fas-transgenic Balb3T3 cells, we tried to obtain inhibitory genes against Fas-mediated apoptosis and identified proto-oncogene c-K-ras. Transient expression of K-Ras mutants revealed that oncogenic mutant K-Ras (RasV12) strongly inhibited, whereas dominant-inhibitory mutant K-Ras (RasN17) enhanced, Fas-mediated apoptosis by inhibiting Fas-triggered activation of caspases without affecting an expression level of Fas. Among the target molecules of Ras, including Raf (mitogen-activated protein kinase kinase kinase [MAPKKK]), phosphatidylinositol 3 (PI-3) kinase, and Ral guanine nucleotide exchange factor (RalGDS), only the constitutively active form of Raf (Raf-CAAX) could inhibit Fas-mediated apoptosis. In addition, the constitutively active form of MAPKK (SDSE-MAPKK) suppressed Fas-mediated apoptosis, and MKP-1, a phosphatase specific for classical MAPK, canceled the protective activity of oncogenic K-Ras (K-RasV12), Raf-CAAX, and SDSE-MAPKK. Furthermore, physiological activation of Ras by basic fibroblast growth factor (bFGF) protected Fas-transgenic Balb3T3 cells from Fas-mediated apoptosis. bFGF protection was also dependent on the activation of the MAPK pathway through Ras. All the results indicate that the activation of MAPK through Ras inhibits Fas-mediated apoptosis in Balb3T3 cells, which may play a role in oncogenesis.

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