NDF/heregulin stimulates the phosphorylation of Her3/erbB3.
Her3/erbB3 has been identified as a third member of the epidermal growth factor receptor (EGFR) family [(1989) Proc. Natl. Acad. Sci. USA 86, 9193-9197; (1990) Proc. Natl. Acad. Sci. USA 87, 4905-4909]. The natural ligand for Her3 has not been identified. Although recently NDF has been proposed as a specific ligand for Her4 [(1993) Nature 366, 473-475; (1993) J. Biol. Chem. 268, 18407-18410], we report here that Her3 was phosphorylated on tyrosine not only in three breast carcinoma cell lines, MDAMB453, MDAMB468 and SKBR3, but also in Her3-transfected CHO cells in response to NDF stimulation. In further studies, cells were reacted with 125I-labeled NDF and then chemically crosslinked. Immunoprecipitation with anti-Her3 revealed a dense high Mw band, greater than 400 kDa. The results suggest that NDF may be a ligand of Her3 and induces receptor hetero-oligomerization.
Kita
Y A
YA
Department of Immunology, Amgen Center, Thousand Oaks, CA 91320.
Barff
J
J
Luo
Y
Y
Wen
D
D
Brankow
D
D
Hu
S
S
Liu
N
N
Prigent
S A
SA
Gullick
W J
WJ
Nicolson
M
M
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D016466:CHO Cells; D002277:Carcinoma / Q000378:metabolism*; D006224:Cricetinae; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D020880:Neuregulins; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020893:Receptor, ErbB-3; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D006023:Glycoproteins; D020880:Neuregulins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D014443:Tyrosine; D066246:ErbB Receptors; D020893:Receptor, ErbB-3