Structural Studies of a New Nuclear Target for EGF Receptor Tyrosine Kinase
Abstract
This project involves structural studies of a nuclear target for the EGE receptor, and the elated Neu/ErbB2 tyrosine kinase, named the CBC for RNA-capped binding protein complex. The CBC consists of two subunits, CBP20 (Mr 18 kDa) and CBP80 (Mr 90 kda), and undergoes a growth factor (EGE, heregulin)-dependent binding of RNAs transcribed by the 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 mucleocytoplasmic transport of U snRNAs which are necessary for the formation of the spliceosome complexes. While, EGF stimulates CBC activity, it is most strongly stimulated by heregulin, an activator of the Neu/ErbB2 tyrosine kinase, and appears to be constitutive in breast cancer where Neu/ErbB2 expression is high. Thus, we believe that the CBC represents an exciting nuclear target for receptor tyrosine kinases, linking growth factor-dependent gene expression to RNA processing. We have solved the atomic structure of the CBC alone and in complex with the cap structure analog m7GpppG at 2.1 A. The atomic structure of this triple complex - represents the second eukaryotic cap binding structure solved to date and reveals interesting aspects of capped RNA binding and regulation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA415658
Entities
People
- Guillermo A. Calero
- Jon Clardy
- Rick Cerione
Organizations
- Cornell University