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10.1042/BJ20110129 http://scihub22266oqcxt.onion/10.1042/BJ20110129 C4398398!4398398!21635223     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\21635223.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Biochem+J 2011 ; 438 (1): 39-51 Nephropedia Template TP {{tp|p=21635223|t=2011. TARGETING THE AUTOLYSIS LOOP OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR WITH CONFORMATION-SPECIFIC MONOCLONAL ANTIBODIES |pdf=|usr=}}{{21635223}} gab.com Text TARGETING THE AUTOLYSIS LOOP OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR WITH CONFORMATION-SPECIFIC MONOCLONAL ANTIBODIES JO: Biochem J http://www.kidney.de/pget.php?&tw=1&pmid=21635223 #FOAvip Tight regulation of serine proteases is essential for their physiological functions and unbalanced states of protease activity have been implicated in a variety of human diseases. One key example is the presence of urokinase-type plasminogen activator (uPA) in different human cancer types, with high levels correlating with a poor prognosis. This observation has stimulated efforts into finding new principles for intervening with uPA?s activity. We have now characterised the so-called autolysis loop in the catalytic domain of uPA as a potential inhibitory target. This loop was found to harbour the epitopes for three conformation-specific monoclonal antibodies, two with a preference for the zymogen form pro-uPA, and one with a preference for active uPA. All three antibodies were shown to have overlapping epitopes, with three common residues being crucial for all three antibodies, demonstrating a direct link between conformational changes of the autolysis loop and the creation of a catalytically mature active site. All three antibodies are potent inhibitors of uPA activity, the two pro-uPA-specific ones by inhibiting conversion of pro-uPA to active uPA and the active uPA-specific antibody by shielding the access of plasminogen to the active site. Furthermore, by immunofluorescence, the conformation-specific antibodies, mAb-112 and mAb-12E6B10, enabled us to selectively stain pro-uPA or active uPA on the surface of cultured cells. Moreover, in various independent model systems, the antibodies inhibited tumour cell invasion and dissemination, providing evidence for the feasibility of pharmaceutical intervention with serine protease activity by targeting surface-loops that undergo conformational changes during zymogen activation. Twit Text FOAVip TARGETING THE AUTOLYSIS LOOP OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR WITH CONFORMATION-SPECIFIC MONOCLONAL ANTIBODIES ????Biochem J http://www.kidney.de/pget.php?&tw=1&pmid=21635223 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=21635223 #FOAvip English Wikipedia <ref>{{Cite pmid|21635223}}</ref> TARGETING THE AUTOLYSIS LOOP OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR WITH CONFORMATION-SPECIFIC MONOCLONAL ANTIBODIES #MMPMID21635223 Botkjaer KA; Fogh S; Bekes EC; Chen Z; Blouse GE; Jensen JM; Mortensen KK; Huang M; Deryugina E; Quigley JP; Declerck PJ; Andreasen PA Biochem J 2011[Aug]; 438 (1): 39-51 PMID21635223show ga Tight regulation of serine proteases is essential for their physiological functions and unbalanced states of protease activity have been implicated in a variety of human diseases. One key example is the presence of urokinase-type plasminogen activator (uPA) in different human cancer types, with high levels correlating with a poor prognosis. This observation has stimulated efforts into finding new principles for intervening with uPA?s activity. We have now characterised the so-called autolysis loop in the catalytic domain of uPA as a potential inhibitory target. This loop was found to harbour the epitopes for three conformation-specific monoclonal antibodies, two with a preference for the zymogen form pro-uPA, and one with a preference for active uPA. All three antibodies were shown to have overlapping epitopes, with three common residues being crucial for all three antibodies, demonstrating a direct link between conformational changes of the autolysis loop and the creation of a catalytically mature active site. All three antibodies are potent inhibitors of uPA activity, the two pro-uPA-specific ones by inhibiting conversion of pro-uPA to active uPA and the active uPA-specific antibody by shielding the access of plasminogen to the active site. Furthermore, by immunofluorescence, the conformation-specific antibodies, mAb-112 and mAb-12E6B10, enabled us to selectively stain pro-uPA or active uPA on the surface of cultured cells. Moreover, in various independent model systems, the antibodies inhibited tumour cell invasion and dissemination, providing evidence for the feasibility of pharmaceutical intervention with serine protease activity by targeting surface-loops that undergo conformational changes during zymogen activation. äTARGETING THE AUTOLYSIS LOOP OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR W(epmc).pdf DeepDyve Pubget Overpricing