Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have described the scaffolding protein FHL2 as a component of focal adhesion structures, to which it is recruited via binding to both alpha- or beta-integrin subunits. Using mesenchymal stem cells from wild-type and FHL2-knockout mice, we show here that inactivation of FHL2 leads to impaired assembly of extracellular matrix proteins on the cell surface and to impaired bundling of focal adhesions. Both altered properties can be restored by reexpression of recombinant FHL2 protein in FHL2-null cells. Molecular analysis of integrin-mediated signaling revealed a higher phosphorylation of FAK at tyrosine 925 in FHL2-knockout cells compared to their wild-type counterpart. Consequently, the activation of the mitogenic kinase ERK was more pronounced in knockout cells on cell adhesion. The growth factor-induced activation of ERK, however, was not altered. The perturbed organization of extracellular matrix on FHL2-null cells was improved when the increased activation of MAPK was inhibited. Our findings point to a role of FHL2 in bundling of focal adhesion structures, in integrin-mediated ERK activation, and subsequently in proper allocation of matrix proteins on the cell surface.
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PMID:Deficiency in the LIM-only protein FHL2 impairs assembly of extracellular matrix proteins. 1835 3

The diagnostic differentiation between canine fibrosarcomas and peripheral nerve sheath tumours (PNSTs) is based on histopathological phenotype. Histological differentiation of these tumours can, however, be challenging and there is a lack of immunohistochemical markers to prove their histogenic origin. To identify possible PNST markers and to further characterize their histogenic origin we compared histologically well-defined canine fibrosarcomas and PNSTs by cDNA microarray analysis. Forty-five annotated gene products were significantly differentially expressed between both tumour types. Seven of these gene products, known to be specifically expressed in neuroectodermal tissues, had higher expression levels in PNSTs: FMN2, KIF1B, GLI1, ROBO1, NMUR2, DOK4 and HMG20B. Conversely, eight genes associated with carcinogenesis had higher expression in fibrosarcomas: FHL2, PLAGL1, FNBP1L, BAG2, HK1, CSK and Cox5A. Comparison of the fibrosarcoma and PNST transcriptome therefore identified PNST phenotype-associated genes involved in neuroectodermal differentiation, which may be useful as diagnostic markers. Furthermore, the genes associated with the fibrosarcoma phenotype may serve as markers to differentiate fibrosarcomas from other tumour types.
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PMID:Canine cutaneous peripheral nerve sheath tumours versus fibrosarcomas can be differentiated by neuroectodermal marker genes in their transcriptome. 2281 16