Constitutively active ErbB4 and ErbB2 mutants exhibit distinct biological activities.
ErbB4 is a member of the epidermal growth factor receptor(EGFR) family of tyrosine kinases, which includes EGFR/ErbB1, ErbB2/HER2/Neu, and ErbB3/HER3. These receptors play important roles both in normal development and in neoplasia. For example, deregulated signaling by ErbB1 and ErbB2 is observed in many human malignancies. In contrast, the roles that ErbB4 plays in tumorigenesis and normal biological processes have not been clearly defined. To identify the biological responses that are coupled to ErbB4, we have constructed three constitutively active ErbB4 mutants. Unlike a constitutively active ErbB2 mutant, the ErbB4 mutants are not coupled to increased cell proliferation, loss of contact inhibition, or anchorage independence in a rodent fibroblast cell line. This suggests that ErbB2 and ErbB4 may play distinct roles in tumorigenesis in vivo.
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907-1333, USA.
Desi J
DJ
Penington
Ianthe
I
Bryant
David J
DJ
Riese
D002448:Cell Adhesion; D002455:Cell Division; D002478:Cells, Cultured / Q000378:metabolism; D003114:Colony-Forming Units Assay; D003260:Contact Inhibition / Q000502:physiology; D017931:DNA Primers / Q000737:chemistry; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D010957:Plasmids; D016133:Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D066247:Receptor, ErbB-4; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D017931:DNA Primers; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; D014443:Tyrosine; C587689:ERBB4 protein, human