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Identification of Heregulin, a Specific Activator of p185 erbB2
Abstract
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 factor family. Scatchard analysis of the binding of recombinant HRG to a breast tumor cell line expressing p185 erb B2 showed a single high affinity binding site [dissociation constant ( K d ) = 105 ± 15 picomolar]. Heregulin transcripts were identified in several normal tissues and cancer cell lines. The HRGs may represent the natural ligands for p185 erb B2 .
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Cited by
Houck, K. A., Leung, D. W., Rowland, A. M., Winer, J., & Ferrara, N. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35712-0 · Cited by 1,127
Neuregulin 1 in neural development, synaptic plasticity and schizophrenia
Mei, L., & Xiong, W.-C. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2392 · Cited by 1,030
Spivak-Kroizman, T., Lemmon, M. A., Dikic, I., Ladbury, J. E., Pinchasi, D., Huang, J., Jaye, M., Crumley, G., Schlessinger, J., & Lax, I. (1994) · Cell · doi:10.1016/0092-8674(94)90032-9 · Cited by 658
Nakajima, M., Sawada, H., Yamada, Y., Watanabe, A., Tatsumi, M., Yamashita, J., Matsuda, M., Sakaguchi, T., Hirao, T., & Nakano, H. (1999) · Cancer · doi:10.1002/(sici)1097-0142(19990501)85:9%3c1894::aid-cncr3%3e3.0.co;2-j · Cited by 494
Heregulin induces tyrosine phosphorylation of HER4/p180erbB4
Plowman, G. D., Green, J. M., Culouscou, J.-M., Carlton, G. W., Rothwell, V. M., & Buckley, S. (1993) · Nature · doi:10.1038/366473a0 · Cited by 441
Metadata
- Authors
- Holmes, W. E., Sliwkowski, M. X., Akita, R. W., Henzel, W. J., Lee, J., Park, J. W., Yansura, D., Abadi, N., Raab, H., Lewis, G. D., Shepard, H. M., Kuang, W.-J., Wood, W. L., Goeddel, D. V., & Vandlen, R. L.
- Venue
- Science
- Published
- 1992-05-22
- Volume
- 256
- Issue
- 5060
- Pages
- 1205-1210
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1973188134
- Cited by
- 962
- References
- 0
- FWCI
- 33.25
- Type
- journal article
- Language
- en
- Open access
- closed
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- Holmes, W. E., Sliwkowski, M. X., Akita, R. W., Henzel, W. J., Lee, J., Park, J. W., Yansura, D., Abadi, N., Raab, H., Lewis, G. D., Shepard, H. M., Kuang, W.-J., Wood, W. L., Goeddel, D. V., & Vandlen, R. L. (1992). Identification of Heregulin, a Specific Activator of p185 erbB2. Science. https://doi.org/10.1126/science.256.5060.1205
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