The juxtamembrane regions of the epidermal growth factor receptor and gp185erbB-2 determine the specificity of signal transduction.
The epidermal growth factor receptor (EGFR) and gp185erbB-2 are closely related tyrosine kinases. Despite extensive sequence and structural homology, these two receptors display quantitative and qualitative differences in their ability to couple with mitogenic signalling pathways. By using chimeric molecules between EGFR and erbB-2, we found that the determinants responsible for the specificity of mitogenic signal transduction are located in the amino-terminal half of the tyrosine kinase domain of either receptor. In the EGFR, mutational analysis within this subdomain revealed that deletion of residues 660 to 667 impaired receptor mitogenic activity without affecting its tyrosine kinase properties. This sequence is therefore likely to contribute to the specificity of substrate recognition by the EGFR kinase.
Laboratory of Molecular and Cellular Biology, National Cancer Institute, Bethesda, Maryland 20892.
O
O
Segatto
F
F
Lonardo
D
D
Wexler
F
F
Fazioli
J H
JH
Pierce
D P
DP
Bottaro
M F
MF
White
P P
PP
Di Fiore
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D014644:Genetic Variation; D005822:Genetic Vectors; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D018719:Erb-b2 Receptor Tyrosine Kinases; D015398:Signal Transduction; D014162:Transfection
D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases