The Frat/GBP (frequently rearranged in T-cell lymphomas/GSK-3-binding protein) protein is a proto-oncogene that regulates the Wnt signalling pathway. (van Amerongen et al., 2004)
The cited paper (Franca-Koh, 2002) noted a correlation between some forms of Frat and GSK3 cellular localization. Without Frat, GSK3 is cytoplasmic. In the presence of Frat, the heterodimer Frat-GSK3 translocates to the nucleus. As Frat is phosphorylated, it was unclear then what mechanism(s) was(were) involved. To investigate the role of Frat, the authors hypothesized that a region of Frat may be involved, not necessarily the whole protein.
They engineered deletion constructs and added an N-terminal FLAG tag for easy affinity purification. They used the symbol delta (Δ) for deletion. The N-terminal region of residues 1 – 129 encompassing Domain 1, i.e. deletion of the C-terminal region is called ΔC; likewise, the C-terminal region of residues 129-274 encompassing Domain 2, i.e. deletion of the N-terminus is called ΔN. They also engineered a green fluorescent protein (GFP) tag fusion protein variant. Here are their constructs as illustrated on Figure 1 of their paper:
I aligned the residue sequence of the murine Frat with the human orthologs: it has 79% identity to human Frat1 and 68% identity to human Frat2. mFrat residues 1 – 129 (ΔC) and 129 – 274 (ΔN) correspond to hFrat1 residues 1 – 132 and 132 – 279, respectively.
Here is a co-crystal structure of GSK3β (N-terminal lobe in orange and C-terminal lobe in cyan) complexed with Frat1 peptide 197-226 (forest green) and an inhibitor (N-(6-(3,4-dihydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)acetamide) (green) as deposited with RCSB as entry 5OY4.pdb . The presence of the inhibitor helps locate the active site in the image of the GSK3b protein kinase.
Franca-Koh, J., Yeo, M., Fraser, E., Young, N. and Dale, T.C. (2002) J. Biol. Chem. 277:43844-43848.
Van Amerongen, R., van der Gulfen, H., Bleeker, F., Jonkers, J. and Berns, A. (2004) J. Biol. Chem. 279:26967-26974.