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)

An HIV-infected man receiving antiretroviral therapy-who also had lupus-like vasculitis and membranous glomerulonephritis (treated with prednisolone and azathioprine), beta-thalassaemia minor trait and post-radiotherapy functional asplenia (mimicking sickle cell disease-induced hyposplenism)-developed focal soft issue and bone infection caused by Salmonella enteritidis at the site of previous mycobacterial infection.
Int J STD AIDS 2008 Jul
PMID:Focal Salmonella enteritidis infection in a patient with HIV infection and other multiple causes of immunodeficiency. 1857 27

The morphology of healthy podocyte foot processes is necessary for maintaining the characteristics of the kidney filtration barrier. In most forms of glomerular disease, abnormal filter barrier function results when podocytes undergo foot process spreading and retraction by remodeling their cytoskeletal architecture and intercellular junctions during a process known as effacement. The cell adhesion protein nephrin is necessary for establishing the morphology of the kidney podocyte in development by transducing from the specialized podocyte intercellular junction phosphorylation-mediated signals that regulate cytoskeletal dynamics. The present studies extend our understanding of nephrin function by showing that nephrin activation in cultured podocytes induced actin dynamics necessary for lamellipodial protrusion. This process required a PI3K-, Cas-, and Crk1/2-dependent signaling mechanism distinct from the previously described nephrin-Nck1/2 pathway necessary for assembly and polymerization of actin filaments. Our present findings also support the hypothesis that mechanisms governing lamellipodial protrusion in culture are similar to those used in vivo during foot process effacement in a subset of glomerular diseases. In mice, podocyte-specific deletion of Crk1/2 prevented foot process effacement in one model of podocyte injury and attenuated foot process effacement and associated proteinuria in a delayed fashion in a second model. In humans, focal adhesion kinase and Cas phosphorylation - markers of focal adhesion complex-mediated Crk-dependent signaling - was induced in minimal change disease and membranous nephropathy, but not focal segmental glomerulosclerosis. Together, these observations suggest that activation of a Cas-Crk1/2-dependent complex is necessary for foot process effacement observed in distinct subsets of human glomerular diseases.
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PMID:Crk1/2-dependent signaling is necessary for podocyte foot process spreading in mouse models of glomerular disease. 2225 1

The Ste20-like kinase, SLK, has diverse cellular functions. SLK mediates organ development, cell cycle progression, cytoskeletal remodeling, cytokinesis, and cell survival. Expression and activity of SLK are enhanced in renal ischemia-reperfusion injury, and overexpression of SLK was shown to induce apoptosis in cultured glomerular epithelial cells (GECs) and renal tubular cells, as well as GEC/podocyte injury in vivo. The SLK protein consists of a N-terminal catalytic domain and an extensive C-terminal domain, which contains coiled-coils. The present study addresses the regulation of SLK activity. Controlled dimerization of the SLK catalytic domain enhanced autophosphorylation of SLK at T183 and S189, which are located in the activation segment. The full-length ectopically- and endogenously-expressed SLK was also autophosphorylated at T183 and S189. Using ezrin as a model SLK substrate (to address exogenous kinase activity), we demonstrate that dimerized SLK 1-373 or full-length SLK can effectively induce activation-specific phosphorylation of ezrin. Mutations in SLK, including T183A, S189A or T193A reduced T183 or S189 autophosphorylation, and showed a greater reduction in ezrin phosphorylation. Mutations in the coiled-coil region of full-length SLK that impair dimerization, in particular I848G, significantly reduced ezrin phosphorylation and tended to reduce autophosphorylation of SLK at T183. In experimental membranous nephropathy in rats, proteinuria and GEC/podocyte injury were associated with increased glomerular SLK activity and ezrin phosphorylation. In conclusion, dimerization via coiled-coils and phosphorylation of T183, S189 and T193 play key roles in the activation and signaling of SLK, and provide targets for novel therapeutic approaches.
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PMID:Regulation of Ste20-like kinase, SLK, activity: Dimerization and activation segment phosphorylation. 2847 47

The worldwide re-emergence of secondary syphilis which happened in the last decade, has led to an increase in primary and secondary syphilis cases, along with the presentation of atypical forms. Nevertheless, reports of renal syphilis with mucosal and/or cutaneous manifestations are nowadays increasing. Typically, secondary syphilis infection in adults causes nephrotic syndrome due to a membranous glomerulonephritis. Here, we report a case of a 30-year-old immunocompetent man presenting with skin rash, oral and perianal erosions and nephritic syndrome. Laboratory investigations revealed a form of membranoproliferative glomerulonephritis secondary to Treponema pallidum infection. Therapy with benzathine penicillin brought prompt and complete remission of the disease. Although well described for congenital syphilis, this histopathologic pattern of renal involvement is very rarely reported in adult patients. In case of detection of an otherwise unexplained nephritic syndrome in sexually active patients with mucosal and/or anal lesions, an unrecognized syphilis infection should be suspected.
Int J STD AIDS 2018 03
PMID:Unusual presentation of secondary syphilis: membranoproliferative glomerulonephritis andmuco-cutaneous lesions. 2895 Jul 64

Several studies have confirmed that the myeloid-derived suppressor cells (MDSCs) are closely associated with autoimmune diseases, but their exact role in these processes remains largely unclear. Here, we investigated the role MDSCs in patients with primary membranous nephropathy (PMN). Compared to healthy controls (HCs), PMN patients showed significantly increased number of HLA-DR-CD11b+CD33+ MDSCs in the peripheral blood, including both CD14+CD66b- monocytic and CD14-CD66b+ granulocytic MDSCs. The frequency of MDSCs was positively correlated with the level of serum anti-phospholipase A2 receptor (anti-PLA2R), 24-h urine protein quantification, and disease activity in PMN patients. Consistently, enhanced T helper 2 (Th2) and T helper 17 (Th17) immune responses were positively associated with plasma anti-PLA2R levels, 24-h urine protein quantification, and the disease activity in PMN patients. Moreover, compared to HCs, MDSCs from PMN patients exhibited significantly elevated arginase-1 (ARG-1) production and increased potential to promote Th17 differentiation in vitro in an ARG-1-dependent manner. This study directly demonstrates a pathogenic role for MDSCs in human PMN and provides a molecular mechanism for the pathogenesis of PMN. Our data show that MDSCs may promote PMN disease progression mainly by enhancing Th17 response. Therefore, MDSCs may be an important diagnostic, therapeutic, and prognostic marker for PMN diseases.
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PMID:Myeloid-Derived Suppressor Cells Promote the Progression of Primary Membranous Nephropathy by Enhancing Th17 Response. 3297 48