The DLG protein is required for the proliferation control in Drosophila epithelia. It is a
member of protein family Membrane Associated Guanylate Kinase Homolog
(MAGUKs), which also contains P55 and CAMGUK. DLG itself is characterized by
protein domains PDZ 1-3, SH3, HOOK, and GUK.DLG protein locates at the septate
junctions of epithelial cells. It not only has function in growth control but also in the
proper organization of the skeleton, the differential localization of membrane proteins,
and the apicobasal polarity of epithelial cells. Null mutations in DLG can cause the
overgrowth of the epithelial cells, and the gene dlg, therefore, works as a tumor
suppressor in cell proliferation control. However, some of these mutations do not affect
other functions of DLG listed above because the mutations in two protein domains PDZ2 and PDZ-3 cause the loss of normal cell proliferation control without affecting other
functions of the DLG protein (Hough! et al. 1997). As we have identified, in human, the
candidate EGF Receptor protein found in database as binding to the PDZ-2 and 3 in DLG
somehow involves in the cancer development. In Coenorhaditis elegans, LET-23, the
homologous structure of EGFR, is also found to bind to LIN-7 and together with the
complex LIN-7/ LIN-2/ LIN-10 works for the growth control (Kaech et al.1998). In
Drosophila, FLIN-7 in complex with FLIN-10, is found to bind to protein receptor DER,
the homolog structure of EGFR, to function in growth control. Because of the fact that
DLG binds to EGFR (human) as well as FLIN-7 binds to DER (Drosophila), the question
is whether there is a competence between DLG and FLIN-7 in binding to DER to be
function in growth control in Drosophila. Moreover, another question is that among three
proteins of MAGUKS family, DLG, CAMGUK, and P55 (this is found to bind with
VELI, homologous structure of FLIN-7, in vertebrates and also in Drosophila), which of
these will appear in the complex of FLIN-7 and FLIN-10 such that the combination
FLIN-7/ (DLG/CAMGUK/P55)/ FLIN-10 as binding to DER will function as
proliferation control in Drosophila. These two questions will be clarified if we can figure
out the protein interactions among the MAGUKS family and the complex FLIN-7/ (?)/
FLIN-10.