Identification of Heregulin, a Specific Activator of p185erbB2

WE Holmes, MX Sliwkowski, RW Akita, WJ Henzel… - Science, 1992 - science.org
WE Holmes, MX Sliwkowski, RW Akita, WJ Henzel, J Lee, JW Park, D Yansura, N Abadi…
Science, 1992science.org
The proto-oncogene designated erb B2 or HER2 encodes a 185-kilodalton transmembrane
tyrosine kinase (p185 erb B2), whose overexpression has been correlated with a poor
prognosis in several human malignancies. A 45-kilodalton protein heregulin-α (HRG-α) that
specifically induced phosphorylation of p185 erb B2 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 …
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-α (HRG-α) 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.
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