Transformation of NIH 3T3 cells by HER3 or HER4 receptors requires the presence of HER1 or HER2.
Members of the epidermal growth factor receptor (EGFR) subfamily of receptor protein tyrosine kinases have been implicated in the pathogenesis of various malignancies. The ability of one EGFR subfamily member to influence, or function synergistically with, another is likely to be a general feature of these receptors. To assess the role of receptor heterodimerization, we analyzed the ability of Neu differentiation factor (NDF) to induce cell growth and transformation of NIH 3T3 cells transfected with different combinations of the EGFR subfamily of receptors. NDF induced mitogenesis, but not transformation, of cells expressing either HER3 or HER4 alone. However, NDF-induced cell transformation was observed when either HER1 or HER2 was coexpressed with HER3 or HER4. In analogous receptor phosphorylation experiments, NDF-induced transphosphorylation appears to be correlated with synergistic transformation of NIH 3T3 cells. Interestingly, transphosphorylation between HER1 and HER4 can be stimulated by either EGF or NDF.
Zhang
K
K
Amgen Inc., Thousand Oaks, California 91320, USA.
Sun
J
J
Liu
N
N
Wen
D
D
Chang
D
D
Thomason
A
A
Yoshinaga
S K
SK
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D020880:Neuregulins; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D014162:Transfection
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D006023:Glycoproteins; D009414:Nerve Growth Factors; D020880:Neuregulins; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C587690:Erbb4 protein, mouse