scholarly journals Regulation of Ephexin1, a Guanine Nucleotide Exchange Factor of Rho Family GTPases, by Fibroblast Growth Factor Receptor-mediated Tyrosine Phosphorylation

2007 ◽  
Vol 282 (42) ◽  
pp. 31103-31112 ◽  
Author(s):  
Yueqiang Zhang ◽  
Takahiro Sawada ◽  
Xuefeng Jing ◽  
Hideyuki Yokote ◽  
Xiaomei Yan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Guanine Nucleotide ◽  
Fibroblast Growth ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Rho Family Gtpases ◽  
Rho Family

scholarly journals Ras activation by insulin and epidermal growth factor through enhanced exchange of guanine nucleotides on p21ras

1993 ◽  
Vol 13 (1) ◽  
pp. 155-162
Author(s):  
R H Medema ◽  
A M de Vries-Smits ◽  
G C van der Zon ◽  
J A Maassen ◽  
J L Bos
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Guanine Nucleotide Exchange Factor ◽  
Nucleotide Binding ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Exchange Factor ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Epidermal Growth

A number of growth factors, including insulin and epidermal growth factor (EGF), induce accumulation of the GTP-bound form of p21ras. This accumulation could be caused either by an increase in guanine nucleotide exchange on p21ras or by a decrease in the GTPase activity of p21ras. To investigate whether insulin and EGF affect nucleotide exchange on p21ras, we measured binding of [alpha-32P]GTP to p21ras in cells permeabilized with streptolysin O. For this purpose, we used a cell line which expressed elevated levels of p21 H-ras and which was highly responsive to insulin and EGF. Stimulation with insulin or EGF resulted in an increase in the rate of nucleotide binding to p21ras. To determine whether this increased binding rate is due to the activation of a guanine nucleotide exchange factor, we made use of the inhibitory properties of a dominant negative mutant of p21ras, p21ras (Asn-17). Activation of p21ras by insulin and EGF in intact cells was abolished in cells infected with a recombinant vaccinia virus expressing p21ras (Asn-17). In addition, the enhanced nucleotide binding to p21ras in response to insulin and EGF in permeabilized cells was blocked upon expression of p21ras (Asn-17). From these data, we conclude that the activation of a guanine nucleotide exchange factor is involved in insulin- and EGF-induced activation of p21ras.

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