Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.2.1.23 (
beta-galactosidase
)
14,648
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hepatoma-derived growth factor
(
HDGF
) has proliferative, angiogenic, and neurotrophic activity. It plays a putative role in the development and progression of cancer. When expressed in cells, the mitogenic activity of
HDGF
depends on its nuclear localization, but it also stimulates proliferation when added to the cell culture medium. A cell surface receptor for
HDGF
has not been identified so far. We investigated the interaction of various purified recombinant
HDGF
fusion proteins with the cell surface of NIH 3T3 fibroblasts. We showed that binding of a
HDGF
-
beta-galactosidase
fusion protein to the cell surface of NIH 3T3 fibroblasts was saturable, occurred with high affinity (K(D) = 14 nm), and had a proliferative effect. We identified a peptide comprising amino acid residues 81-100 within the amino-terminal part of
HDGF
that bound to the cell surface of NIH 3T3 cells with saturation and affinity values similar to those of
HDGF
. When added to primary human fibroblasts, this peptide stimulated proliferation. Substitution of a single amino acid (K96A) within this peptide was sufficient to abolish its binding to the cell surface and its proliferative activity. In contrast, when expressed transiently in NIH 3T3 cells, a
HDGF
-
beta-galactosidase
fusion protein in which amino acid residues 81-100 were deleted still had proliferative activity, whereas a fusion protein containing only the 81-100 peptide did not. Our results suggest the existence of a plasma membrane-located
HDGF
receptor for which signaling depends on amino acid residues 81-100 of
HDGF
. This region differs from the one that has been recently identified to be essential for mitogenic activity depending on the nuclear localization of
HDGF
. Thus,
HDGF
exerts its proliferative activity via two different pathways.
...
PMID:Hepatoma-derived growth factor. Significance of amino acid residues 81-100 in cell surface interaction and proliferative activity. 1565 45
