An extra cysteine proximal to the transmembrane domain induces differential cross-linking of p185neu and p185neu.
The neu proto-oncogene encodes a receptor tyrosine kinase (p185) that is closely related to the epidermal growth factor receptor. It has been proposed that receptor tyrosine kinases are activated through oligomerization. Because this clustering model predicts that oligomerization of receptors is sufficient to activate them, we determined if p185 can be activated by introducing an extra cysteine proximal to the transmembrane domain. This should induce inter-receptor disulfide bonding and, according to the clustering model, activate the receptor. This amino acid substitution enhanced recovery of both normal and transforming neu proteins as dimers, with normal p185 recovered predominantly as monomers and transforming p185* as dimers. However, the cysteine substitution did not affect the transforming activity of the two proteins.
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510.
H
H
Cao
L
L
Bangalore
C
C
Dompé
B J
BJ
Bormann
D F
DF
Stern
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D003432:Cross-Linking Reagents; D003545:Cysteine / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D051379:Mice; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases
D003432:Cross-Linking Reagents; D003545:Cysteine; D009841:Oligonucleotides; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases