The enzymatic activity of phosphoglucose isomerase is not required for its cytokine function.
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.
Tsutsumi
Soichi
S
Karmanos Cancer Institute, Wayne State University School of Medicine, 110 East Warren, Detroit, MI 48201, USA.
Gupta
Suresh K
SK
Hogan
Victor
V
Tanaka
Nobutada
N
Nakamura
Kazuo T
KT
Nabi
Ivan R
IR
Raz
Avraham
A
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
D016207:Cytokines; D018121:Receptors, Cytokine; C555000:AMFR protein, human; D060285:Receptors, Autocrine Motility Factor; D044767:Ubiquitin-Protein Ligases; D005956:Glucose-6-Phosphate Isomerase