The Role of Protein Kinase in Human Synovial Fibroblast Growth

1995 ◽  
Vol 210 (3) ◽  
pp. 1066-1075 ◽  
Author(s):  
K. Migita ◽  
K. Eguchi ◽  
T. Tsukada ◽  
Y. Kawabe ◽  
T. Aoyagi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Synovial Fibroblast ◽  
Fibroblast Growth ◽  
Human Synovial Fibroblast

scholarly journals The Docking Protein Gab1 Is an Essential Component of an Indirect Mechanism for Fibroblast Growth Factor Stimulation of the Phosphatidylinositol 3-Kinase/Akt Antiapoptotic Pathway

2004 ◽  
Vol 24 (13) ◽  
pp. 5657-5666 ◽  
Author(s):  
Betty Lamothe ◽  
Masashi Yamada ◽  
Ute Schaeper ◽  
Walter Birchmeier ◽  
Irit Lax ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Fibroblast Growth Factor ◽  
Critical Role ◽  
Mitogen Activated Protein Kinase ◽  
Fibroblast Growth ◽  
Indirect Mechanism ◽  
Docking Protein ◽  
Stimulation Of

ABSTRACT The docking protein Gab1 has been implicated as a mediator of multiple signaling pathways that are activated by a variety of receptor tyrosine kinases and cytokines. We have previously proposed that fibroblast growth factor 1 (FGF1) stimulation of tyrosine phosphorylation of Gab1 and recruitment of phosphatidylinositol (PI) 3-kinase are mediated by an indirect mechanism in which the docking protein fibroblast receptor substrate 2α (FRS2α) plays a critical role. In this report, we explore the role of Gab1 in FGF1 signaling by using mouse embryo fibroblasts (MEFs) derived from Gab1−/− or FRS2α−/− mice. We demonstrate that Gab1 is essential for FGF1 stimulation of both PI 3-kinase and the antiapoptotic protein kinase Akt, while FGF1-induced mitogen-activated protein kinase (MAPK) stimulation is not affected by Gab1 deficiency. To test the indirect mechanism for FGF1 stimulation of PI 3-kinase and Akt, we use a chimeric docking protein composed of the membrane targeting signal and the phosphotyrosine-binding domain of FRS2α fused to the C-terminal portion of Gab1, the region including the binding sites for the complement of signaling proteins that are recruited by Gab1. We demonstrate that expression of the chimeric docking protein in Gab1−/− MEFs rescues PI 3-kinase and the Akt responses, while expression of the chimeric docking protein in FRS2α−/− MEFs rescues stimulation of both Akt and MAPK. These experiments underscore the essential role of Gab1 in FGF1 stimulation of the PI 3-kinase/Akt signaling pathway and provide further support for the indirect mechanism for FGF1 stimulation of PI 3-kinase involving regulated assembly of a multiprotein complex.

Downregulation of lymphocyte activity and human synovial fibroblast growth in rheumatoid arthritis by triptolide

1999 ◽  
Vol 47 (3) ◽  
pp. 144-153 ◽  
Author(s):  
Kwok-keung Tong ◽  
Dan Yang ◽  
Eric Yuk-Tat Chan ◽  
Peter Kwong-Yuen Chiu ◽  
Kam-Shing Yau ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fibroblast ◽  
Fibroblast Growth ◽  
Human Synovial Fibroblast ◽  
Lymphocyte Activity
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