Abstract
Cellular receptors for blood proteases regulate chemotaxis, extracellular proteolysis, and growth behavior of normal and malignant cells. Binding of the coagulation protease factor Xa to leukocytes is contributed by a recently identified molecule, denominated Effector cell Protease Receptor-1 (EPR-1). Monoclonal antibodies were generated against EPR-1+ MOLT13 lymphocytes and selected for reactivity with lymphocyte surface proteins by flow cytometry and with affinity-purified EPR-1 in Western blots. Antibody-based functional cloning of the cDNA for EPR-1 reveals the sequence of a novel molecule encoded by a prominent 1.9-kilobase mRNA. The cDNA predicts a glycoprotein of 337 amino acids, characterized by a unique cysteine-rich extracellular module, a single membrane-spanning domain, and a serine-rich (26%) cytoplasmic tail featuring at least 15 potential phosphorylation sites. Genetically engineered EPR-1 transfectants were recognized by monoclonal antibodies to EPR-1 and bound 125I-factor Xa in a specific and saturable manner (Kd approximately 10-15 nM). In the absence of factor V/Va, EPR-1 transfectants promoted prothrombin activation in a factor Xa concentration-dependent reaction, inhibited by a monoclonal antibody to EPR-1. These findings define EPR-1 as a novel cell surface receptor for factor Xa potentially implicated in protease-dependent cellular effector functions.
Highlights
Cell Surface Receptor for the Protease FactorXa*For factorXa, distinct from factorVNa. Activated rabbit alveolar macrophages expressa factor Xa receptor, only in p a r t immunologically related to factor VNa, that promotes prothrombinactivation in the absence of factor VNa [13]
From the Departments of Immumlogy and Vascular Biology, Scripps Research Institute, receptor, denominated Effector cell Frotease Receptor-1 (EPRl), was dynamicallyregulated by cell activation,with an 8-10
Activated rabbit alveolar macrophages expressa factor Xa receptor, only in p a r t immunologically related to factor VNa, that promotes prothrombinactivation in the absence of factor VNa [13]
Summary
For factorXa, distinct from factorVNa. Activated rabbit alveolar macrophages expressa factor Xa receptor, only in p a r t immunologically related to factor VNa, that promotes prothrombinactivation in the absence of factor VNa [13]. Using (Received for publication, October 11, 1993, and in revised form, monoclonalantibody(mAb)l strategy, similar findingswere December 8, 1993) independently reported on human monocytes and monocytic. From the Departments of Immumlogy and Vascular Biology, Scripps Research Institute, receptor, denominated Effector cell Frotease Receptor-1 (EPRl), was dynamicallyregulated by cell activation,with an 8-10-. Cellular receptors for blood proteases regulate che- the factor VdfactorXa interaction (ll), bindingof factor Xa to motaxis, extracellular proteolysis, and growth behavEioPrR-1 promoted prothrombin activation(141, or the generation t-orPtawieefnoreicdonnnretesosneebgpratllmeyrseyneocaettfiledrelRoaaadeewstnnfceeodtedirpfcfaimaytegorctdaaloetcloiamilnXmgrc(senatEotitavtElrPoeniytRPctycuRl-eae1lle1wnu)l,.+sdki.MtdohBecwonM yinlniotytoOedhmmcsiLislniopTnacgnh1faoof3aotniflenctldtayriyhtnitmybeeEt-uippbfctsfhuooeuedoadrcricgtiffeoyauibsertclyedaesc-aepEllrtbompnPeoferonoRee-vintsnnei-soa1ltiecelotllyrnruymtacenoiiesmdsfudmarpittafheelatimedecceabbcp.trDyeradoNTnfdieuAhnune.gccplTtptyrsirhoocioonetmefpaaralrfesroacesytclu-eotdisolnntetrsirpnruIeiegcXnncatdedunaiperdcctenaotmtitrovemafafmotteEhircomPahnftRaaa(cl1nE-it16iaoPs)nrhmRXac-sase1aotl,lfnitspeoihnoxwea---. The cDNAfor EPRl reveals the sequencoef a novel molecule encoded by a prominent 1.9-kilobasemRNk The
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