Functional Study of Brk-mediated EPS8 Phosphorylation
Date Issued
2010
Date
2010
Author(s)
Lin, Ching-Jung
Abstract
Breast tumor kinase (Brk), an Src-like nonreceptor tyrosine kinase, is
overexpressed in breast cancer and several other cancer types. Previous studies in our
lab indicate that Brk promotes Rac activation and cell migration by phosphorylating
paxillin and p190RhoGAP-A. In this thesis, we report epidermal growth factor receptor
pathway substrates 8 (EPS8) as a new interacting partner and substrate of Brk. In
addition, we identified seven tyrosine residues, i.e., Y454, Y485, Y491, Y498, Y525,
Y723, Y774, as major sites targeted by Brk. Surprisingly, this Brk-induced EPS8
tyrosine phosphorylation plays inhibitory roles in cell adhesion, spreading and
migration. These effects correlate with a downregulation of Rac1 activity and
upregulation of actin stress fiber formation. Thus, our findings suggest that EPS8
tyrosine phosphorylation promotes its actin bundling activity or downregulates the
formation of EPS8-Abi1-SOS1 complex, which processes a GEF activity toward Rac.
Our study also reveals that Brk can elicit both inhibitory and stimulatory effects on Rac
activity, via distinct downstream effectors. Such feature of Brk might facilitate a
temporally or spatially specific regulation on cell migration.
Subjects
Brk
EPS8
tyrosine phosphorylation
migration
SDGs
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-99-R97b46015-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):55d00290c74556fdb5ee2404f4feefad