title: The enzymatic activity of phosphoglucose isomerase is not required for its cytokine function.
abstract: PGI is a housekeeping gene encoding phosphoglucose isomerase (PGI) a glycolytic enzyme that also functions as a cytokine (autocrine motility factor (AMF)/neuroleukin/maturation factor) upon secretion from the cell and binding to its 78 kDa seven-transmembrane domain receptor (gp78/AMF-R). PGI contains a CXXC motif, characteristic of redox proteins and possibly evolutionarily related to the CC and CXC motif of the chemokine gene family. Using site-directed mutagenesis, single- and double-deletion (CXC, CC) mutants were created by deleting amino acids 331 and 332 of human PGI, respectively. The mutant proteins lost their enzymatic activity; however, neither of the deletions augmented the proteins' binding affinity to the receptor and all maintained cytokine function. The results demonstrate that the enzymatic activity of PGI is not essential for either receptor binding or cytokine function of human PGI.
authors.affiliation: Karmanos Cancer Institute, Wayne State University School of Medicine, 110 East Warren, Detroit, MI 48201, USA.
authors.forename: Soichi
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Victor
authors.initials: V
authors.lastname: Hogan
authors.forename: Nobutada
authors.initials: N
authors.lastname: Tanaka
authors.forename: Kazuo T
authors.initials: KT
authors.lastname: Nakamura
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Nabi
authors.forename: Avraham
authors.initials: A
authors.lastname: Raz
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D016207:Cytokines / Q000378:metabolism*; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D060285:Receptors, Autocrine Motility Factor; D018121:Receptors, Cytokine / Q000378:metabolism; D017384:Sequence Deletion; D044767:Ubiquitin-Protein Ligases
chemical_list: D016207:Cytokines; D018121:Receptors, Cytokine; C555000:AMFR protein, human; D060285:Receptors, Autocrine Motility Factor; D044767:Ubiquitin-Protein Ligases; D005956:Glucose-6-Phosphate Isomerase