Fer () is a tyrosine-protein kinase that acts downstream of cell surface receptors for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell adhesion, cell migration and chemotaxis [, ]. In non-small cell lung cancer cells, Fer kinase expression has been linked to cell invasion and tumour metastasis []. It also acts downstream of EGFR (EGF receptor) to promote activation of NF-kappa-B and cell proliferation [].
Fer () is a tyrosine-protein kinase that acts downstream of cell surface receptors for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell adhesion, cell migration and chemotaxis [, ]. In non-small cell lung cancer cells, Fer kinase expression has been linked to cell invasion and tumour metastasis []. It also acts downstream of EGFR (EGF receptor) to promote activation of NF-kappa-B and cell proliferation [].This entry represents the F-BAR domain of Fer. F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization [, ].
Cortactin is a key regulator of actin polymerisation in response to tyrosine kinase signalling []. It was first identified as a tyrosine-phosphorylated protein in v-Src infected fibroblasts []. It contains several domains: an N-terminal acidic (NTA) domain, a central repeat region and a C-terminal Src homology 3 (SH3) domain. The central repeat region binds to actin filaments, the NTA domain binds to the Arp2/3 complex and the SH3 domain interacts with N-WASp, Arg and WIP []. When activated, cortactin can recruit Arp2/3 complex to existing actin filaments to nucleate a new actin filament. Cortactin is involved in the regulation of cell migration, lamellipodia formation, invadopodia formation and endocytosis []. Cortactin can be phosphorylated by Src at several sites, and also binds directly to the SH2 domain of SRC. The non-receptor kinases, such as Fyn, Syk and Fer may also play a role in cortactin tyrosine phosphorylation. The structure of cortactin has been solved [].
FCH domain is a short conserved region of around 60 amino acids first described as a region of homology between FER and CIP4 proteins []. In the CIP4 protein the FCH domain binds to microtubules []. The FCH domain is always found N-terminally and is followed by a coiled-coil region. The FCH and coiled-coil domains are structurally similar to Bin/amphiphysin/RVS (BAR) domains []. They are α-helical membrane-binding modules that function in endocytosis, regulation of the actin cytoskeleton and signalling []. Proteins containing an FCH domain can be divided in 3 classes []:A subfamily of protein kinases usually associated with an SH2 domain:Fps/fes (Fujimani poultry sarcoma/feline sarcoma) proto-oncogenes. They are non-receptor protein-tyrosine kinases preferentially expressed in myeloid lineage. The viral oncogene has an unregulated kinase activity which abrogates the need for cytokines and influences differentiation of haematopoietic progenitor cells.Fes related protein (fer). It is an ubiquitously expressed homologue of Fes.Adaptor proteins usually associated with a C-terminal SH3 domain:Schizosaccharomyces pombe CDC15 protein. It mediates cytoskeletal rearrangements required for cytokinesis. It is essential for viability.CD2 cytoplasmic domain binding protein.Mammalian Cdc42-interacting protein 4 (CIP4). It may act as a link between Cdc42 signaling and regulation of the actin cytoskeleton.Mammalian PACSIN proteins. A family of cytoplasmic phosphoproteins playing a role in vesicle formation and transport.A subfamily of Rho-GAP proteins:Mammalian RhoGAP4 proteins. They may down-regulate Rho-like GTPases in hematopoietic cells.Yeast RHO GTPase-activating protein RGD1 (also known as YBR260C).Caenorhabditis elegans hypothetical protein ZK669.1.
