Immunobiological Aspects of erbB Receptors in Breast Cancer.
Abstract
The general problem of assembly, activation and disabling the receptor complexes of the erbB family is being studied and its relevance to cancer ascertained. We have analyzed how mutants of the endodomain of pl85neu affect the function of other heteromeric or homomeric partners of the receptor ensemble. We have studied molecular forms of neuregulin found in a transformed human lymphoid cell line that seem able to activate p185 even in the absence of erbB 3 or 4. We analyzed the creation of enabled or disabled receptor complexes built of the EGFR and mutant or normal forms of p185 to determine receptor inhibition pathways. Lack of an endodomain of p185 was found to disable the EGF receptor's kinase activity and limit transforming abilities even when additional ligands such as EGF were added. The biochemical pathway most inhibited was the P13 kinase pathway. The scope of the major findings was that a component of the receptor complex called a signal inhibitory receptor polypeptide (SIRP) could be activated by the disabled complex and was, in part, responsible for limiting P13 kinase activity. Finally, we are developing an understanding of receptor inhibition that involves complex activation of pathways such as SIRP and the modulation of proteasome function, in addition to receptor internalization.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA372252
Entities
People
- Mark I. Greene
Organizations
- University of Pennsylvania