Evidence that the V832M E-cadherin germ-line missense mutation does not influence the affinity of alpha -catenin for the cadherin/catenin complex.
Mutations in E-cadherin are associated with a number of diseases, and have been shown to contribute to disease progression. In particular, 50% of hereditary diffuse gastric cancer cases have inactivating mutations in the E-cadherin gene. An interesting mutation near the beta-catenin-binding site on the cytoplasmic domain of E-cadherin (V832M) was recently reported that produces full-length protein, but exhibits decreased binding of alpha -catenin to the cadherin/catenin complex. The study was done by transfecting mutant E-cadherin into Chinese hamster ovary fibroblast cells. Here we show that the previously reported characteristics of this mutation do not apply to human epithelial cells expressing this mutant protein and suggest that the mechanism whereby the V832M mutation in human E-cadherin promotes gastric cancer is not yet understood.
Curtis
Matthew W
MW
University of Nebraska Medical Center, Department of Pathology and Microbiology, Omaha, Nebraska, USA.
Ly
Quan P
QP
Wheelock
Margaret J
MJ
Johnson
Keith R
KR
D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D018095:Germ-Line Mutation / Q000235:genetics*; D018698:Glutamic Acid / Q000235:genetics*; D006801:Humans; D050505:Mutant Proteins / Q000378:metabolism; D020125:Mutation, Missense / Q000235:genetics*; D011485:Protein Binding; D014633:Valine / Q000235:genetics*; D051178:alpha Catenin / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; D050505:Mutant Proteins; D051178:alpha Catenin; D051176:beta Catenin; D018698:Glutamic Acid; D014633:Valine