Disease relevance of Fert2

• At the molecular level, Fer was found to associate with ERK1/2 and this interaction was intensified under hypoxia [1].

High impact information on Fert2

• Closing in on the biological functions of Fps/Fes and Fer [2].
• Here, we report that in mouse bone marrow-derived mast cells, Fer kinase is activated downstream of activated Fc epsilon RI and activated Kit receptor, and this activation is abolished in cells homozygous for a kinase-inactivating mutation in Fer (fer(DR/DR)) [3].
• Fer kinase is required for sustained p38 kinase activation and maximal chemotaxis of activated mast cells [3].
• Thus, Fer is required for maximal p38 kinase activation to promote the chemotaxis of activated mast cells [3].
• While Fer-deficient cells showed similar activation of the Erk mitogen-activated protein (MAP) kinases, p38 MAP kinase activation was less sustained than that in wild-type cells [3].

Biological context of Fert2

• Therefore, Fer likely serves a redundant role in regulating cell growth, cell adhesion, retinal development, and spermatogenesis but is required for efficient phosphorylation of cortactin [4].
• The ubiquitous Fer protein-tyrosine kinase has been proposed to regulate diverse processes such as cell growth, cell adhesion, and neurite outgrowth [4].
• To gain insight into the biological function of Fer, we have targeted the fer locus with a kinase-inactivating missense mutation (fer(D743R)) [4].
• The restoration of Fer kinase activity in fer(DR/DR) mast cells resulted in prolonged p38 kinase activation and increased antigen-mediated cell migration of sensitized mast cells [3].
• In this study, knock-in mice harboring kinase-inactivating mutations in both fps and fer alleles were used to assess functional redundancy between Fps and Fer kinases in regulating hematopoiesis [5].

Anatomical context of Fert2

• No differences were observed in overall cellularity of bone marrow, spleen, or thymus in the absence of Fer activity [4].
• Herein, we show that insulin up-regulates the levels of the fer mRNA and Fer protein in myoblasts that undergo insulin-induced myogenic differentiation [6].
• Although no differences in the overall number of granulocyte/monocyte colony-forming progenitors were observed, qualitative differences in myeloid colonies from compound mutant mice suggested a role for Fps and Fer kinases in regulating cell-cell adhesion or a skewing in cellularity of colonies [5].
• Circulating levels of neutrophils, erythrocytes, and platelets were elevated in compound mutant mice compared to wild-type controls, suggesting that hematopoiesis is deregulated in the absence of Fps and Fer kinases [5].
• These data provide the first evidence for a biological role for Fer in regulation of leukocyte recruitment during the innate immune response [7].

Associations of Fert2 with chemical compounds

• Moreover, insulin directs the interaction of Fer with members of the Janus family of tyrosine kinases (Jak)-Stat3 signaling pathway [6].
• Here we examined the role of Fer in modulating leucocyte recruitment and epithelial barrier function in the gut in response to lipopolysaccharide (LPS) [8].

Physical interactions of Fert2

• Fer interacts with cadherin indirectly, through p120ctn [9].

Other interactions of Fert2

• This report represents the first description of a common signaling pathway activating Fer and Fps/Fes [3].
• Although no major defects were observed in degranulation, leukotriene biosynthesis, and cytokine secretion, Fer-deficient cells displayed increased adhesion and decreased motility upon activation of Fc epsilon RI and the Kit receptor [3].
• The cytoplasmic distribution of TMF/ARA160 was accompanied by its transient association with the tyrosine kinase Fer and with Stat3, which underwent proteasomal degradation under those conditions [10].
• Furthermore, this activation was suppressed following inhibition of JAKs (Janus kinases) but not inhibition of Fer, IGF1-R, or kinases of the c-Src family [11].
• On the other hand, targeted disruption of the Fer kinase or pharmacological inhibition of Abl had no effect [12].

Analytical, diagnostic and therapeutic context of Fert2

• Fer is a downstream effector of insulin and mediates the activation of signal transducer and activator of transcription 3 in myogenic cells [6].
• Tyrosine phosphorylation of cortactin after N-cadherin ligation was strongly reduced in fibroblasts expressing only catalytically inactive Fer (D743R), compared with wild-type cells [13].

References