[Frontiers in Bioscience 16, 3146-3155, June 1, 2011]

Structure and regulation of the c-Fes protein-tyrosine kinase

Sabine Hellwig, Thomas E. Smithgall

Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, U.S.A.

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Relationship to transforming retroviral oncogenes
4. Antibodies to v-Fps/Fes oncoproteins identify a novel tyrosine kinase in hematopoietic cells
5. Overall domain organization
6. The unique N-terminal region of Fes contains F-BAR/coiled-coil oligomerization domains involved in the regulation of kinase activity
7. The Fes SH2 domain is required for full kinase and biological activities and mediates substrate recruitment and subcellular localization
8. Kinase domain autophosphorylation is required for full kinase and biological activities of Fps/Fes proteins
9. Structural biology of the c-Fes SH2-kinase region provides a mechanistic basis for positive regulation of kinase activity by direct SH2 domain interaction
10. Summary and conclusions
11. Acknowledgements
12. References

1. ABSTRACT

The c-Fes protein-tyrosine kinase is the normal cellular ortholog of several avian and feline retroviral oncoproteins. Unlike its transforming viral counterparts, c-Fes tyrosine kinase activity is tightly regulated in vivo through a mechanism involving coiled-coil oligomerization domains and other unique structural features found in its long N-terminal region. This review is focused on the regulatory features and structural biology of c-Fes, which has been implicated in normal cellular growth regulation, the innate immune response, and tumorigenesis.