Accession Number:

ADA383149

Title:

Structural Studies of a New Nuclear Target for EGF Receptor Tyrosine Kinases

Descriptive Note:

Annual rept. 15 Jul 1999-14 Jul 2000

Corporate Author:

CORNELL UNIV ITHACA NY

Personal Author(s):

Report Date:

2000-08-01

Pagination or Media Count:

18.0

Abstract:

This project involves structural studies of an interesting new nuclear target for the EGF receptor, and the related NeuErbB2 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 NeuErbB2 tyrosine kinase, and appears to be constitutive in breast cancer cells where NeuErbB2 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.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE