Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit.
We recently reported that a 44 kd glycoprotein secreted by transformed fibroblasts stimulates tyrosine phosphorylation of the product of the neu proto-oncogene and induces differentiation of mammary tumor cells to milk-producing, growth-arrested cells. A partial amino acid sequence of the protein, termed Neu differentiation factor (NDF), enabled cloning of the corresponding complementary DNA. The deduced structure of the precursor of NDF indicated that it is a transmembrane protein whose extracellular portion contains an EGF-like domain that probably functions as a receptor recognition site. In addition, the ectodomain contains one immunoglobulin homology unit. Despite the lack of a recognizable hydrophobic signal peptide at the N-terminus, a recombinant NDF, like the natural molecule, is released into the medium of transfected COS-7 cells in a biologically active form. Northern blot analysis indicated the existence of several NDF transcripts, the major ones being 1.8, 2.6, and 6.7 kb in size. Transformation by the ras oncogene dramatically elevated the expression of NDF in fibroblasts.
Wen
D
D
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Peles
E
E
Cupples
R
R
Suggs
S V
SV
Bacus
S S
SS
Luo
Y
Y
Trail
G
G
Hu
S
S
Silbiger
S M
SM
Levy
R B
RB
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004815:Epidermal Growth Factor / Q000737:chemistry; D015870:Gene Expression; D006023:Glycoproteins / Q000737:chemistry; D007136:Immunoglobulins / Q000737:chemistry; D008024:Ligands; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D020880:Neuregulins; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D016415:Sequence Alignment; D012995:Solubility
D004247:DNA; D004815:Epidermal Growth Factor; D006023:Glycoproteins; D007136:Immunoglobulins; D008024:Ligands; D008562:Membrane Glycoproteins; D020880:Neuregulins; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins