Identification of heregulin, a specific activator of p185erbB2.
The proto-oncogene designated erbB2 or HER2 encodes a 185-kilodalton transmembrane tyrosine kinase (p185erbB2), whose overexpression has been correlated with a poor prognosis in several human malignancies. A 45-kilodalton protein heregulin-alpha (HRG-alpha) that specifically induced phosphorylation of p185erbB2 was purified from the conditioned medium of a human breast tumor cell line. Several complementary DNA clones encoding related HRGs were identified, all of which are similar to proteins in the epidermal growth factor family. Scatchard analysis of the binding of recombinant HRG to a breast tumor cell line expressing p185erbB2 showed a single high affinity binding site [dissociation constant (Kd) = 105 +/- 15 picomolar]. Heregulin transcripts were identified in several normal tissues and cancer cell lines. The HRGs may represent the natural ligands for p185erbB2.
Holmes
W E
WE
Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA 94080.
Sliwkowski
M X
MX
Akita
R W
RW
Henzel
W J
WJ
Lee
J
J
Park
J W
JW
Yansura
D
D
Abadi
N
N
Raab
H
H
Lewis
G D
GD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003062:Codon; D003470:Culture Media; D004268:DNA-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000235:genetics; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D020880:Neuregulins; D015345:Oligonucleotide Probes; D010766:Phosphorylation; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D003062:Codon; D003470:Culture Media; D004268:DNA-Binding Proteins; D004815:Epidermal Growth Factor; D006023:Glycoproteins; D020880:Neuregulins; D015345:Oligonucleotide Probes; D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human