Structural Studies of a New Nuclear Target for EGF Receptor Tyrosine Kinases
Abstract
This project involves structural studies of an interesting new nuclear target for the EGF receptor, and the related Neu/ErbB2 tyrosine kinase, named the CEO for RNA-capped binding protein complex. The CEO consists of two subunits, CEP2O (Mr 20 kDa) and CEPSO (Mr 80 kDa), and undegoes a growth factor (EGF, heregulin)-dependent binding of RNAs transcribed by RNA polymerase II at a 5' cap structure that consists of a guanosine residue methylated at the N7 position. This represents a first key step in the cap-dependent splicing of precursor messenger RNA (mRNA) and in the nucleocytoplasmic transport of U snRNAs which are necessary for the formation of spliceosome complexes. While CEO activity is stimulated by EGF, it is most strongly stimulated by heregulin, an activator of the Neu/ErbB2 tyrosine kinase, and appears to be constitutive in breast cancer cells where Neu/ErbB2 expression is high. Thus, we believe that the CEO represents an exciting nuclear target for receptor tyrosine kinases, linking growth factor-dependent gene expression to RNA processing. We have obtained (2.35 A) X-ray diffraction data for the CEO. Further experiments using heavy atom derivatives are being conducted at this time and will provide us with enough information to be able to solve the structure of the CEO.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA383149
Entities
People
- Guillermo Calero
Organizations
- Cornell University