[Membrane receptors and cell transformation].
Here I discuss quantitative and qualitative activation of several receptor-type molecules in tumor cells. Recently we have shown that EGF-R gene is frequently mutated in human glioblastoma. Mutant EGF-R had a 801-bp deletion within the ligand binding domain, and showed a ligand-independent, constitutive elevation of tyrosine kinase activity. This EGF-R mutation is detected only in glioma and associated with gene amplification, suggesting a relationship in the molecular mechanism between deletion mutation and initiation of gene amplification in these cases. Secondly I have shown an activation of mouse CD43 gene by amplification and rearrangement in erythroleukemia cell lines. Intracellular domain of CD43 has no kinase domain but a highly conserved structure among mammals, probably interacting with intracellular signal transducers. Recently CD43 has been demonstrated to be specifically associated with a cell-adhesion molecule ICAM-1. Thus, CD43-ICAM-1 system might be a new type of cytokine system which regulate cell-proliferation through cell-cell interaction. In addition, activation of EpoR and v-mpl is also discussed.
Shibuya
M
M
Department of Genetics, University of Tokyo.
D000818:Animals; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D009857:Oncogenes; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*
D016207:Cytokines; D011971:Receptors, Immunologic