FES

This gene encodes the human cellular counterpart of a feline sarcoma retrovirus protein with transforming capabilities. The gene product has tyrosine-specific protein kinase activity and that activity is required for maintenance of cellular transformation. Its chromosomal location has linked it to a specific translocation event identified in patients with acute promyelocytic leukemia but it is also involved in normal hematopoiesis as well as growth factor and cytokine receptor signaling. Alternative splicing results in multiple variants encoding different isoforms.[provided by RefSeq, Jan 2009]

Full Name

FES Proto-Oncogene, Tyrosine Kinase

Research Area

Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28.

Biological Process

Cell adhesion Source: GO_Central
Cell differentiation Source: GO_Central
Cellular response to vitamin D Source: ARUK-UCL
Centrosome cycle Source: Ensembl
Chemotaxis Source: GO_Central
Innate immune response Source: GO_Central
Microtubule bundle formation Source: Ensembl
Peptidyl-tyrosine phosphorylation Source: UniProtKB
Positive regulation of actin cytoskeleton reorganization Source: UniProtKB
Positive regulation of microtubule polymerization Source: UniProtKB
Positive regulation of monocyte differentiation Source: ARUK-UCL
Positive regulation of myeloid cell differentiation Source: UniProtKB
Positive regulation of neuron projection development Source: UniProtKB
Protein autophosphorylation Source: UniProtKB
Regulation of cell adhesion Source: UniProtKB
Regulation of cell differentiation Source: UniProtKB
Regulation of cell motility Source: UniProtKB
Regulation of cell population proliferation Source: UniProtKB
Regulation of cell shape Source: UniProtKB
Regulation of mast cell degranulation Source: UniProtKB
Regulation of vesicle-mediated transport Source: UniProtKB
Transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central

Cellular Location

Golgi apparatus; Cell membrane; Cytoskeleton; Cytosol; Cytoplasmic vesicle; Focal adhesion. Distributed throughout the cytosol when the kinase is not activated. Association with microtubules requires activation of the kinase activity. Shuttles between focal adhesions and cell-cell contacts in epithelial cells. Recruited to the lateral cell membrane in polarized epithelial cells by interaction with phosphorylated EZR. Detected at tubular membrane structures in the cytoplasm and at the cell periphery.

Involvement in disease

Has been shown to act as proto-oncogene in some types of cancer, possibly due to abnormal activation of the kinase. Has been shown to act as tumor suppressor in other types of cancer. Expressed and present as activated kinase in a subset of acute myeloid leukemia patients; promotes survival of leukemia cells (PubMed:20111072). Expression is absent in K562 leukemia cells; ectopic expression of FSP/FES restores myeloid differentiation (PubMed:2656706). May function as tumor suppressor in colorectal cancer; expression is reduced or absent in samples from some colon cancer patients (PubMed:16455651). May function as tumor suppressor in melanoma by preventing melanoma cell proliferation; expression is reduced or absent in samples from some melanoma patients (PubMed:28463229). Ectopic expression of FSP/FES suppresses anchorage-independent growth in colon cancer cell lines (PubMed:16455651). Up-regulated in prostate cancer, and might be a predictor of recurrence after radical surgery (PubMed:16455651). May promote growth of renal carcinoma cells (PubMed:19082481).

PTM

Autophosphorylated on Tyr-713. Phosphorylated by LYN in response to FCER1 activation. Phosphorylated by HCK.