Disease relevance of Fes

• Finally, Sema3A-induced growth cone collapse of dorsal root ganglion neurons was suppressed by expression of Fes kinase-negative mutants [1].
• We have also demonstrated that activated Fps/Fes causes hemangioma formation in vivo, independently of Flk1, as a result of increasing vascular progenitor density [2].
• The onc gene (v-fes) of the acutely transforming feline sarcoma virus (Snyder-Theilen strain) has homologous cellular sequences (c-fes) in all vertebrate species, including humans [3].
• Human gene (c-fes) related to the onc sequences of Snyder-Theilen feline sarcoma virus [3].
• We isolated from a human DNA library recombinant phages containing overlapping c-fes sequences [3].

High impact information on Fes

• Closing in on the biological functions of Fps/Fes and Fer [4].
• Abnormal Stat activation, hematopoietic homeostasis, and innate immunity in c-fes-/- mice [5].
• To determine the role of Fes in embryonic development and hematopoiesis, we engineered a null mutation of the murine c-fes locus. c-fes-/- mice are viable but not born in the expected Mendelian ratios [5].
• The c-fes protooncogene encodes a nonreceptor tyrosine kinase (Fes) implicated in cytokine receptor signal transduction, neutrophil survival, and myeloid differentiation [5].
• Live born c-fes-/- mice exhibit lymphoid/myeloid homeostasis defects, compromised innate immunity, and increased Stat activation in response to GM-CSF and IL-6 signaling [5].

Biological context of Fes

• There was no association between tumor incidence and genotype at the D7Rp2, Fes, or Int-2 loci [6].
• Genetic and physical mapping of the fitness 1 (fit1) locus within the Fes-Hbb region of mouse chromosome 7 [7].
• Interleukin-4 induces association of the c-fes proto-oncogene product with phosphatidylinositol-3 kinase [8].
• We previously showed that FcepsilonRI aggregation caused a rapid increase in phosphorylation of both Fer and Fps/Fes kinases in bone marrow-derived mast cells [9].
• This study identifies physiological, cellular, and molecular defects that contribute to the hyperinflammatory phenotype in Fps/Fes null mice [10].

Anatomical context of Fes

• Further studies with mast cells derived from fps/fes-deficient mice will be required to provide insight into the role of Fps/Fes in mast cell activation [11].
• These results suggest that Fps/Fes may act synergistically with Flk1 to modulate hemangioblast differentiation into the endothelium [2].
• Expression of the activated Fps/Fes protein in Flk1-deficient embryonic stem (ES) cells rescued their contribution to the developing vascular endothelium in vivo by using ES cell-derived chimeras [2].
• Activated Fps/Fes partially rescues the in vivo developmental potential of Flk1-deficient vascular progenitor cells [2].
• Insulin-like growth factor I receptor gene is concordant with c-Fes protooncogene and mouse chromosome 7 in somatic cell hybrids [12].

Associations of Fes with chemical compounds

• Involvement of Fes/Fps tyrosine kinase in semaphorin3A signaling [1].
• Fps/Fes-null mice were healthy and fertile, displayed slightly reduced numbers of bone marrow myeloid progenitors and circulating mature myeloid cells, and were more sensitive to lipopolysaccharide (LPS) [13].
• Further examination of downstream signaling demonstrates that kinase-inactive Fes inhibits the recruitment of phosphoinositide 3-kinase to the activated IL-4 receptor complex and decreases the activation of p70(S6k) kinase in response to IL-4 [14].
• The choline phosphate-containing alkyllysophospholipids (ALPs) had little or moderate effect on the proliferation and none on the viability of NIH 3T3 clone 7, and sublines transformed by raf (NIH/9IV #5), fes (Fes 1), src (Src 1) and mos (Mos 1) oncogenes [15].
• Atipamezole (3 mg/kg), mCPP (3 mg/kg), and h/r-CRF (.3, 1 microg) did not affect FPS, but increased startle independently from the presence of the cue [16].

Physical interactions of Fes

• We have previously shown that 151 base pairs of c-fes 5'-flanking sequences are sufficient for myeloid cell-specific expression and include functional binding sites for Sp1, PU.1, and a novel nuclear factor (Heydemann, A., Juang, G., Hennessy, K., Parmacek, M. S., and Simon, M. C. (1996) Mol. Cell. Biol. 16, 1676-1686) [17].

Regulatory relationships of Fes

• Taken together, our findings suggest that Fes links Sema3A signals to CRMP-CRAM, and that NP-1 negatively regulates PlexA1 activation by Fes in resting condition [1].
• Activated Fps/Fes tyrosine kinase regulates erythroid differentiation and survival [18].
• Using COS-7 cells as a model system, we observed that Fes strongly colocalizes with microtubules in vivo when activated via coiled-coil mutation or by coexpression with an active Src family kinase [19].
• The myeloid-cell-specific c-fes promoter is regulated by Sp1, PU.1, and a novel transcription factor [20].

Other interactions of Fes

• Consistent with previous studies of Pecam-1-deficient mast cells, we observe an exaggerated degranulation response in mast cells lacking Fer/Fps kinases at low antigen dosages [9].
• This report represents the first description of a common signaling pathway activating Fer and Fps/Fes [11].
• Moreover, some loci (e.g., Fes and Mod-2) which are close to c in the mouse appear to be on human chromosomes other than 11 [21].
• The anemic phenotype in fps(MF) mice suggests that downregulation of Fps/Fes activity might be required for terminal erythroid differentiation [18].
• P-Selectin expression was also elevated on the surface of Fps/Fes-null platelets in response to CRP [22].

Analytical, diagnostic and therapeutic context of Fes

• Truncation of c-fes via gene targeting results in embryonic lethality and hyperproliferation of hematopoietic cells [23].
• The mouse homologs of the cellular oncogenes c-Ha-ras-1 of Harvey sarcoma virus and c-fes of feline sarcoma virus were both mapped to chromosome 7 by Southern blot analysis of hamster-mouse somatic cell hybrid DNAs [24].
• PCR amplification of the as yet unsequenced murine c-fes IVS3 and IVS4 showed they are about 50% longer than their human and feline homologs [25].
• In all xenografts, a 3.0 kb c-fes/fps mRNA was present [26].
• Coimmunoprecipitation and immunofluorescence microscopy showed that the N-terminal Fes/CIP4 homology (FCH) domain is involved in Fes interaction with soluble unpolymerized tubulin [19].

References