Fes/Fps and Fer are the only two members of a unique family of cytoplasmic protein tyrosine kinases. Fes and Fer contain a central Src homology-2 domain and a carboxy-terminal tyrosine kinase catalytic domain. They are structurally distinguished from other members of cytoplasmic protein tyrosine kinase subfamilies by the presence of amino-terminal Fer/CIP4 homology and coiled-coil domains. Fes/Fps was originally identified as an oncogene from avian and feline retroviruses. Human c-Fes has been implicated in myeloid, vascular endothelial and neuronal cell differentiation. Mutations may activate the Fps kinase and thereby contribute to cancer. However, recent data strongly suggests that the c-Fes protein-tyrosine kinase is a tumor suppressor rather than a dominant oncogene in colorectal cancer.
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