Premium
Grb7 binds to Hax‐1 and undergoes an intramolecular domain association that offers a model for Grb7 regulation
Author(s) -
SiamakpourReihani Sharareh,
Peterson Tabitha A.,
Bradford Andrew M.,
Argiros Haroula J.,
Haas Laura Lowell,
Lor Siamee N.,
Haulsee Zachary M.,
Spuches Anne M.,
Johnson Dennis L.,
Rohrschneider Larry R.,
Shuster Charles Brad,
Lyons Barbara A.
Publication year - 2011
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.1062
Subject(s) - signal transducing adaptor protein , focal adhesion , microbiology and biotechnology , signal transduction , grb2 , sh2 domain , phosphorylation , tyrosine phosphorylation , chemistry , biology
Adaptor proteins mediate signal transduction from cell surface receptors to downstream signaling pathways. The Grb7 protein family of adaptor proteins is constituted by Grb7, Grb10, and Grb14. This protein family has been shown to be overexpressed in certain cancers and cancer cell lines. Grb7‐mediated cell migration has been shown to proceed through a focal adhesion kinase (FAK)/Grb7 pathway, although the specific participants downstream of Grb7 in cell migration signaling have not been fully determined. In this study, we report that Grb7 interacts with Hax‐1, a cytoskeletal‐associated protein found overexpressed in metastatic tumors and cancer cell lines. Additionally, in yeast 2‐hybrid assays, we show that the interaction is specific to the Grb7‐RA and ‐PH domains. We have also demonstrated that full‐length Grb7 and Hax‐1 interact in mammalian cells and that Grb7 is tyrosine phosphorylated. Isothermal titration calorimetry measurements demonstrate the Grb7‐RA‐PH domains bind to the Grb7‐SH2 domain with micromolar affinity, suggesting full‐length Grb7 can exist in a head‐to‐tail conformational state that could serve a self‐regulatory function. Copyright © 2010 John Wiley & Sons, Ltd.