Binding specificities and affinities of egf domains for ErbB receptors.
ErbB receptor activation is a complex process and is dependent upon the type and number of receptors expressed on a given cell. Previous studies with defined combinations of ErbB receptors expressed in mammalian cells have helped elucidate specific biological responses for many of the recognized gene products that serve as ligands for these receptors. However, no study has examined the binding of these ligands in a defined experimental system. To address this issue, the relative binding affinities of the egf domains of eleven ErbB ligands were measured on six ErbB receptor combinations using a soluble receptor-ligand binding format. The ErbB2/4 heterodimer was shown to bind all ligands tested with moderate to very high affinity. In contrast, ErbB3 showed much more restrictive ligand binding specificity and measurable binding was observed only with heregulin, neuregulin2beta, epiregulin and the synthetic heregulin/egf chimera, biregulin. These studies also revealed that ErbB2 preferentially enhances ligand binding to ErbB3 or ErbB4 and to a lesser degree to ErbB1.
Jones
J T
JT
Genentech, Inc., Department of Molecular Oncology, South San Francisco, CA 94080, USA.
Akita
R W
RW
Sliwkowski
M X
MX
D000595:Amino Acid Sequence; D066259:Betacellulin; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006133:Growth Substances / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020880:Neuregulins; D018739:Oncogene Proteins v-erbB / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
C587851:BTC protein, human; D066259:Betacellulin; C587852:Btc protein, mouse; D002352:Carrier Proteins; D006023:Glycoproteins; D006133:Growth Substances; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D046911:Macromolecular Substances; C106766:NRG2 protein, human; C486357:NRG3 protein, human; D009414:Nerve Growth Factors; D020880:Neuregulins; C491453:Nrg2 protein, mouse; D018739:Oncogene Proteins v-erbB; D011994:Recombinant Proteins; D016211:Transforming Growth Factor alpha; C108365:biregulin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors