The erbB3 gene product is a receptor for heregulin.
ErbB3 is a member of the epidermal growth factor (EGF) receptor subfamily of receptor tyrosine kinases and is believed to be a receptor for an unknown ligand. We have tested the possibility that heregulin, a growth factor possessing an EGF-like domain, is a ligand for ErbB3. We have found that the iodinated recombinant EGF-like domain of heregulin-beta 1 (125I-rHRG beta 1(177-244) bound specifically to insect cell-expressed bovine ErbB3 with a dissociation constant of 0.85 nM. Moreover, 125I-rHRG beta 1(177-244) bound to NIH3T3 fibroblasts stably transfected with bovine erbB3 with a dissociation constant of 60 pM, but did not bind to parental cells. 125I-rHRG beta 1(177-244) could be chemically cross-linked to a 170-180 kDa protein in erbB3-transfected fibroblasts, and the cross-linked product could be immunoprecipitated with antibodies specific for ErbB3. Finally, rHRG beta 1 stimulated the tyrosine phosphorylation of both ErbB3 and endogenous p185erbB2/neu in transfectants but not in parental cells. We conclude that ErbB3 is a receptor for HRG and is capable of mediating HRG-stimulated tyrosine phosphorylation of itself and p185erbB2/neu in cells that express both receptors.
Carraway
K L
KL
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts.
Sliwkowski
M X
MX
Akita
R
R
Platko
J V
JV
Guy
P M
PM
Nuijens
A
A
Diamonti
A J
AJ
Vandlen
R L
RL
Cantley
L C
LC
Cerione
R A
RA
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D003001:Cloning, Molecular; D066246:ErbB Receptors / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D006023:Glycoproteins / Q000378:metabolism*; D007457:Iodine Radioisotopes; D051379:Mice; D008969:Molecular Sequence Data; D009036:Moths; D020890:Neuregulin-1; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020893:Receptor, ErbB-3; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D002352:Carrier Proteins; D006023:Glycoproteins; D007457:Iodine Radioisotopes; D020890:Neuregulin-1; D011518:Proto-Oncogene Proteins; C087230:heregulin beta1; D014443:Tyrosine; D066246:ErbB Receptors; D020893:Receptor, ErbB-3