FES/FPS (feline sarcoma) and FER (FES-related) proteins are the only two members of a subfamily of non-receptor tyrosine kinases. Due to their unique structures, they are distinguished from other non-receptor tyrosine kinase families. FES/FPS was originally identified as an oncogene.
Both FES and FER share similar structures, including an amino-terminal FCH domain, three regions of predicted coiled-coils, a SH2 domain and a C-terminal kinase domain. The FCH domain has been found in numerous proteins involved in the regulation of cytoskeletal rearrangements and vesicular transport. The predicted coiled-coil domains mediate the formation of homotrimers in FES and pentamer or higher-order oligomers in FER. The conserved SH2 domain is responsible for protein-protein interactions and is thought to mediate interactions with putative substrates or regulators. Evidence has shown that tight interaction between the kinase domain and the SH2 domain is essential for FES function. At least two phosphorylation sites were identified within the kinase domains of FES and FER. Both FES and FER can be substrates of other protein tyrosine kinases as the downstream effector of signals transduced from cell-surface receptors.
Since expression of FES was originally identified in haematopoietic lineages, studies of FES biological roles were mainly focused on signaling downstream of cytokine-receptor superfamily members. For example, interleukin-2 induced cells showed increased phosphorylation of FES. Additionally, FES is found to be abundantly expressed in macrophages and neutrophils, which suggests a role of FES in inflammation.
|FES Kinase list|
|FES/Feline sarcoma oncogene|