scholarly journals Epidermal Growth Factor Stimulates Extracellular-Signal Regulated Kinase Phosphorylation of a Novel Site on Cytoplasmic Dynein Intermediate Chain 2

2013 ◽  
Vol 14 (2) ◽  
pp. 3595-3620 ◽  
Author(s):  
Ashok Pullikuth ◽  
Aysun Ozdemir ◽  
Daviel Cardenas ◽  
Evangeline Bailey ◽  
Nicholas Sherman ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cytoplasmic Dynein ◽  
Extracellular Signal Regulated Kinase ◽  
Dynein Intermediate Chain ◽  
Extracellular Signal ◽  
Epidermal Growth ◽  
Kinase Phosphorylation ◽  
Intermediate Chain

scholarly journals Phosphorylation of Rac1 T108 by Extracellular Signal-Regulated Kinase in Response to Epidermal Growth Factor: a Novel Mechanism To Regulate Rac1 Function

2013 ◽  
Vol 33 (22) ◽  
pp. 4538-4551 ◽  
Author(s):  
Junfeng Tong ◽  
Laiji Li ◽  
Barbara Ballermann ◽  
Zhixiang Wang
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Rho Gtpases ◽  
Fluorescent Protein ◽  
Phosphorylation Site ◽  
Kinase Assay ◽  
Nucleotide Exchange ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Epidermal Growth

Accumulating evidence has implicated Rho GTPases, including Rac1, in many aspects of cancer development. Recent findings suggest that phosphorylation might further contribute to the tight regulation of Rho GTPases. Interestingly, sequence analysis of Rac1 shows that Rac1 T108 within the106PNTP109motif is likely an extracellular signal-regulated kinase (ERK) phosphorylation site and that Rac1 also has an ERK docking site,183KKRKRKCLLL192(D site), at the C terminus. Indeed, we show here that both transfected and endogenous Rac1 interacts with ERK and that this interaction is mediated by its D site. Green fluorescent protein (GFP)-Rac1 is threonine (T) phosphorylated in response to epidermal growth factor (EGF), and EGF-induced Rac1 threonine phosphorylation is dependent on the activation of ERK. Moreover, mutant Rac1 with the mutation of T108 to alanine (A) is not threonine phosphorylated in response to EGF.In vitroERK kinase assay further shows that pure active ERK phosphorylates purified Rac1 but not mutant Rac1 T108A. We also show that Rac1 T108 phosphorylation decreases Rac1 activity, partially due to inhibiting its interaction with phospholipase C-γ1 (PLC-γ1). T108 phosphorylation targets Rac1 to the nucleus, which isolates Rac1 from other guanine nucleotide exchange factors (GEFs) and hinders Rac1's role in cell migration. We conclude that Rac1 T108 is phosphorylated by ERK in response to EGF, which plays an important role in regulating Rac1.

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