Hb. Hoff et al., DBI-1, A NOVEL GENE-RELATED TO THE NOTCH FAMILY, MODULATES MITOGENIC RESPONSE TO INSULIN-LIKE-GROWTH-FACTOR-1, Experimental cell research, 238(2), 1998, pp. 359-370
The insulin-like growth factor 1 (IGF-1) receptor has been found to tr
ansform fibroblast cells when overexpressed. The removal of 108 aa fro
m the C-terminus of the IGF-1 receptor abolishes the transforming abil
ity of the receptor without affecting its ability to induce cell growt
h. The availability of this mutant receptor provides a means to examin
e the changes in gene expression which take place during transformatio
n, solely in response to an increased number of IGF-1 receptors. Using
differential display, we have examined differences in gene expression
between cells expressing a wild-type, transforming IGF-1 receptor and
cells expressing a C-terminally truncated, nontransforming IGF-1 rece
ptor. We have cloned a novel 6.3-kb cDNA transcript (DBI-1) which is e
xpressed at much lower levels in cells containing the wild-type IGF-1
receptor. The predicted protein sequence of DBI-1 contains seven EGF-l
ike repeats, which bear >90% sequence identity to the rat Notch 2 prot
ein. The cDNA also contains a potential DEAD box in the C-terminal reg
ion. The DBI-1 message is detected at relatively high levels in cardia
c tissue and at lower levels in lung, liver, and kidney. Antibodies ge
nerated to a unique region of the DBI-1 protein recognize a protein of
88 kDa, which is localized in the nucleus. Overexpression of DBI-1 in
cells which contain the wild-type IGF-1 receptor diminishes the mitog
enic response to IGF-1. (C) 1998 Academic Press.