PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 21640771-5 2011 After administration, FK506 and CsA mainly distribute within erythrocytes owing to the presence into these cells of immunophilins that bind the drugs with very high affinity (FKBP12 for FK506 and cyclophilin A for CsA); therefore, a new strategy aimed to increase the amount of FK506/CsA carried by erythrocytes by increasing the intra-erythrocytic concentration of the respective binding proteins has been developed. Tacrolimus 22-27 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 175-181 21640771-5 2011 After administration, FK506 and CsA mainly distribute within erythrocytes owing to the presence into these cells of immunophilins that bind the drugs with very high affinity (FKBP12 for FK506 and cyclophilin A for CsA); therefore, a new strategy aimed to increase the amount of FK506/CsA carried by erythrocytes by increasing the intra-erythrocytic concentration of the respective binding proteins has been developed. Tacrolimus 186-191 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 175-181 21640771-5 2011 After administration, FK506 and CsA mainly distribute within erythrocytes owing to the presence into these cells of immunophilins that bind the drugs with very high affinity (FKBP12 for FK506 and cyclophilin A for CsA); therefore, a new strategy aimed to increase the amount of FK506/CsA carried by erythrocytes by increasing the intra-erythrocytic concentration of the respective binding proteins has been developed. Tacrolimus 186-191 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 175-181 21640771-9 2011 Moreover, FK506 released from FKBP12-RBC is able to be up-taken by T lymphocytes and inhibit IL-2 expression in vitro as free administered drug. Tacrolimus 10-15 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 30-36 19103144-7 2009 Second, specific protection from exogenous protease of FKBP12 by FK506 and Hsp90 fragments by radicicol were observed. Tacrolimus 65-70 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 55-61 21423799-4 2011 Specifically, CsA and FK506 bind to intracellular proteins, principally cyclophilin A and FKBP12, respectively, and thereby inhibit the phosphatase calcineurin (Cn). Tacrolimus 22-27 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 90-96 19154728-6 2009 When cell lysate was treated with and without MTI, tacrolimus and FKBP12, FKBP12 could increase calcineurin inhibition by tacrolimus and reverse the MTI antagonism for both MTIs. Tacrolimus 51-61 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 74-80 19154728-6 2009 When cell lysate was treated with and without MTI, tacrolimus and FKBP12, FKBP12 could increase calcineurin inhibition by tacrolimus and reverse the MTI antagonism for both MTIs. Tacrolimus 122-132 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 66-72 19154728-6 2009 When cell lysate was treated with and without MTI, tacrolimus and FKBP12, FKBP12 could increase calcineurin inhibition by tacrolimus and reverse the MTI antagonism for both MTIs. Tacrolimus 122-132 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 74-80 19154728-7 2009 These results demonstrate that FKBP12 can be rate limiting for calcineurin inhibition at high tacrolimus concentrations and that the antagonism of sirolimus and everolimus on tacrolimus based immune suppression is mediated via saturation of FKBP12. Tacrolimus 94-104 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 31-37 19154728-7 2009 These results demonstrate that FKBP12 can be rate limiting for calcineurin inhibition at high tacrolimus concentrations and that the antagonism of sirolimus and everolimus on tacrolimus based immune suppression is mediated via saturation of FKBP12. Tacrolimus 175-185 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 241-247 18492692-15 2008 FK506 removed FKBP12 from its binding to the TGF-beta-receptor. Tacrolimus 0-5 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 14-20 8591053-4 1995 The target of the cyclophilin A-cyclosporine A and FKBP12-FK506 complexes is calcineurin, a protein phosphatase required for signaling via the T-cell receptor. Tacrolimus 58-63 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 51-57 8794888-2 1996 CsA and FK506 associate with intracellular binding proteins (i.e., CsA with cyclophilin A and FK506 with FKBP12) to form protein/drug complexes that suppress the immune system by preventing activation of T cells in response to antigen presentation. Tacrolimus 8-13 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 105-111 8794888-2 1996 CsA and FK506 associate with intracellular binding proteins (i.e., CsA with cyclophilin A and FK506 with FKBP12) to form protein/drug complexes that suppress the immune system by preventing activation of T cells in response to antigen presentation. Tacrolimus 94-99 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 105-111 8794888-4 1996 In previous studies, we identified calcineurin mutations that block binding by the cyclophilin A/CsA or FKBP12/FK506 complexes and thereby render yeast cells resistant to the antifungal effects of CsA or FK506. Tacrolimus 111-116 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 104-110 8794888-4 1996 In previous studies, we identified calcineurin mutations that block binding by the cyclophilin A/CsA or FKBP12/FK506 complexes and thereby render yeast cells resistant to the antifungal effects of CsA or FK506. Tacrolimus 204-209 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 104-110 8786538-1 1996 FK-506 blocks T cell activation by preventing lymphokine gene transcription through formation of a complex with FKBP12 that inhibits calcineurin phosphatase activity. Tacrolimus 0-6 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 112-118 7514503-1 1994 FK506-binding protein (FKBP12) was originally identified as the cytosolic receptor for the immunosuppressant drugs FK506 and rapamycin. Tacrolimus 0-5 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 23-29 7529023-8 1994 The interaction between FKBP-12 (FK506 binding protein) and the ryanodine-binding Ca2+ channel may be an essential link in the chain of events by which FK506 alters Ca(2+)-dependent cellular processes. Tacrolimus 33-38 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 24-31 7575502-1 1995 The molecular complex formed by the immunosuppressant FK506 and the immunophilin protein FKBP12 potently inhibits the Ca2+/calmodulin-activated protein phosphatase calcineurin. Tacrolimus 54-59 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 89-95 7518461-1 1994 The immunosuppressant FK-506 (tacrolimus) forms a complex with a ubiquitous intracellular receptor, FK-506 binding protein (FKBP12), and this complex inhibits the heterodimeric Ca2+/calmodulin-dependent phosphatase, calcineurin, an essential component of the T-cell receptor signal transduction pathway. Tacrolimus 22-28 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 124-130 7518461-1 1994 The immunosuppressant FK-506 (tacrolimus) forms a complex with a ubiquitous intracellular receptor, FK-506 binding protein (FKBP12), and this complex inhibits the heterodimeric Ca2+/calmodulin-dependent phosphatase, calcineurin, an essential component of the T-cell receptor signal transduction pathway. Tacrolimus 30-40 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 124-130 7518461-6 1994 To assess the role of the autoinhibitory domain in regulating the interaction of CaN with the FK-506.FKBP12 complex, we reconstituted wild type and mutant phosphatase heterodimers using in vitro transcribed and translated subunits. Tacrolimus 94-100 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 101-107 7518461-7 1994 Association of the reconstituted calcineurin heterodimers with FKBP12 was dependent on FK-506. Tacrolimus 87-93 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 63-69 7518461-8 1994 In the case of the wild type heterodimer, association with the FK-506.FKBP12 complex was also dependent upon Ca2+; however, mutant catalytic subunits, in which the autoinhibitory domains were deleted, associated with the drug-binding protein complex in the presence of 10 mM EGTA. Tacrolimus 63-69 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 70-76 7518461-9 1994 These results indicate that the conserved autoinhibitory domain regulates both Ca(2+)-dependent phosphatase activity and association with the FK-506.FKBP12 complex. Tacrolimus 142-148 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 149-155 7518678-1 1994 Tacrolimus(FK506) is a strong immuno-suppressant and shows its activity through inhibiting IL-2 mRNA transcription by forming pentameric complex with intracellular receptor(FK506 binding protein 12 kDa or FKBP12), Ca2+, calmodulin, and calcineurin. Tacrolimus 0-10 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 205-211 7518678-1 1994 Tacrolimus(FK506) is a strong immuno-suppressant and shows its activity through inhibiting IL-2 mRNA transcription by forming pentameric complex with intracellular receptor(FK506 binding protein 12 kDa or FKBP12), Ca2+, calmodulin, and calcineurin. Tacrolimus 11-16 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 205-211 7514503-5 1994 FK506 or rapamycin, inhibitors of FKBP12 isomerase activity, reverse these stabilizing effects. Tacrolimus 0-5 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 34-40 7684925-4 1993 Two largely nonpolar, structurally related macrolide ligands, tacrolimus (also known as FK506) and rapamycin, each bind with high affinity to a common site on a small FK506 binding protein (FKBP-12) and inhibit its peptidylprolyl cis-trans-isomerase activity. Tacrolimus 62-72 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 190-197 7510408-2 1994 Changing tyrosine-82 to phenylalanine in FKBP-12 abolishes protein-ligand hydrogen bond interactions in the FKBP-12 complexes with tacrolimus or rapamycin and leads to a large apparent enthalpic stabilization of binding in both H2O and D2O. Tacrolimus 131-141 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 41-48 7510408-2 1994 Changing tyrosine-82 to phenylalanine in FKBP-12 abolishes protein-ligand hydrogen bond interactions in the FKBP-12 complexes with tacrolimus or rapamycin and leads to a large apparent enthalpic stabilization of binding in both H2O and D2O. Tacrolimus 131-141 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 108-115 7684925-4 1993 Two largely nonpolar, structurally related macrolide ligands, tacrolimus (also known as FK506) and rapamycin, each bind with high affinity to a common site on a small FK506 binding protein (FKBP-12) and inhibit its peptidylprolyl cis-trans-isomerase activity. Tacrolimus 88-93 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 190-197 1379588-4 1992 We have identified, however, three FKBP12 surface residues (Asp-37, Arg-42, and His-87) proximal to a solvent-exposed segment of bound FK506 that may be direct contacts in the calcineurin complex. Tacrolimus 135-140 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 35-41 1379588-0 1992 Charged surface residues of FKBP12 participate in formation of the FKBP12-FK506-calcineurin complex. Tacrolimus 74-79 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 28-34 1379588-0 1992 Charged surface residues of FKBP12 participate in formation of the FKBP12-FK506-calcineurin complex. Tacrolimus 74-79 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 67-73 1379588-1 1992 The mechanism of FK506 immunosuppression has been proposed to proceed by formation of a tight-binding complex with the intracellular 12-kDa FK506-binding protein (FKBP12). Tacrolimus 17-22 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 163-169 7683641-0 1993 FKBP12-FK506 complex inhibits phosphatase activity of two mammalian isoforms of calcineurin irrespective of their substrates or activation mechanisms. Tacrolimus 7-12 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 0-6 7683641-1 1993 The interaction of calcineurin (Ca2+/calmodulin-dependent protein phosphatase) with the potent immunosuppressive agent FK506 and its 12 kDa isoform binding protein (FKBP12) was investigated. Tacrolimus 119-124 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 165-171 7683641-3 1993 Calcineurin phosphatase activity was inhibited by the FKBP12-FK506 complex irrespective of the substrate or the enzyme activation mechanism. Tacrolimus 61-66 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 54-60 7683641-4 1993 FK506 and FKBP-12 inhibited calcineurin in a concentration-dependent manner, and complete inhibition of the phosphatase activity appeared to require a molar excess of FKBP12-FK506 complex. Tacrolimus 174-179 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 10-17 7683641-4 1993 FK506 and FKBP-12 inhibited calcineurin in a concentration-dependent manner, and complete inhibition of the phosphatase activity appeared to require a molar excess of FKBP12-FK506 complex. Tacrolimus 174-179 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 167-173 7683641-6 1993 Direct binding studies with [3H]dihydro-FK506 suggest that the ratio of FKBP12-FK506 complex to calcineurin in vivo when IL2 production is inhibited is well correlated with the ratio when calcineurin phosphatase activity is inhibited in vitro. Tacrolimus 40-45 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 72-78 7683641-7 1993 These results suggest that calcineurin is a relevant cellular target of FK506 when bound to FKBP-12. Tacrolimus 72-77 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 92-99 1379588-5 1992 Site-directed mutagenesis of two of these residues decreases the affinity of FKBP12-FK506 for calcineurin (Ki) from 6 nM for wild-type FKBP12 to 3.7 microM for a R42K/H87V double mutant, without affecting the peptidylprolyl isomerase activity or FK506 affinity of the mutant protein. Tacrolimus 84-89 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 77-83 1379588-5 1992 Site-directed mutagenesis of two of these residues decreases the affinity of FKBP12-FK506 for calcineurin (Ki) from 6 nM for wild-type FKBP12 to 3.7 microM for a R42K/H87V double mutant, without affecting the peptidylprolyl isomerase activity or FK506 affinity of the mutant protein. Tacrolimus 84-89 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 135-141 1379588-5 1992 Site-directed mutagenesis of two of these residues decreases the affinity of FKBP12-FK506 for calcineurin (Ki) from 6 nM for wild-type FKBP12 to 3.7 microM for a R42K/H87V double mutant, without affecting the peptidylprolyl isomerase activity or FK506 affinity of the mutant protein. Tacrolimus 246-251 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 77-83 1379588-6 1992 These FKBP12 mutations along with several substitutions on FK506 known to affect calcineurin binding form a roughly 100-A2 region of the FKBP12-FK506 complex surface that is likely to be within the calcineurin binding site. Tacrolimus 59-64 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 137-143 1379588-6 1992 These FKBP12 mutations along with several substitutions on FK506 known to affect calcineurin binding form a roughly 100-A2 region of the FKBP12-FK506 complex surface that is likely to be within the calcineurin binding site. Tacrolimus 144-149 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 6-12 1379588-6 1992 These FKBP12 mutations along with several substitutions on FK506 known to affect calcineurin binding form a roughly 100-A2 region of the FKBP12-FK506 complex surface that is likely to be within the calcineurin binding site. Tacrolimus 144-149 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 137-143 1279908-3 1992 Yeast FKBP-13 is homologous to human FKBP-13 (52% amino acid identity) and to FKBP-12, the major cytosolic receptor for FK506. Tacrolimus 120-125 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 78-85 35563498-12 2022 While hyperosmolarity alone facilitates TGF-beta superfamily signaling, FK506 further enhances signaling by releasing the FKBP12 break from the type I receptor to improve collagenous marker expression. Tacrolimus 72-77 FKBP prolyl isomerase 1A pseudogene 2 Homo sapiens 122-128