The neurotrophic factor neuroleukin is 90% homologous with phosphohexose isomerase

Chaput, Mariella; Claes, Victor; Portetelle, Daniel; Cludts, Isabelle; Cravador, A.; Burny, Arsène; Gras, Hélène; Tartar, André

doi:10.1038/332454a0

Cited by 258 publications

(130 citation statements)

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“…Molecular cloning and sequencing have identified PGI as a motility factor: i.e., autocrine motility factor (AMF; ref. 5), also known as and neuroleukin (6) or maturation factors (7). AMF/PGI is also a multifunctional cytokine that exhibits multifunctional growth factor-like activity via a unique cognate 78 kDa (gp78) seven-transmembrane glycoprotein receptor (autocrine motility factor receptor, AMFR; ref.…”

Section: Introductionmentioning

confidence: 99%

Autocrine Motility Factor Signaling Enhances Pancreatic Cancer Metastasis

Tsutsumi

Yanagawa

Shimura

et al. 2004

Clinical Cancer Research

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Purpose: Autocrine motility factor (AMF)/phosphoglucose isomerase (PGI) is a ubiquitous cytosolic enzyme that plays a key role in glycolysis. AMF/PGI is also a multifunctional protein that acts in the extracellular milieu as a potent mitogen/cytokine. Increased expression of AMF/PGI and its receptor has been found in a wide spectrum of malignancies and is associated with cancer progression and metastasis. Recent studies indicated that AMF is induced by hypoxia and enhances the random motility of pancreatic cancer cells. In the present study, the role and regulation of AMF in the growth and metastasis of pancreatic cancer cells were determined.Experimental Design: In this study, we assessed whether overexpression of AMF in human pancreatic cancer cells enhances the liver metastasis using an orthotopic mouse tumor model. We also investigated the intracellular signal transduction pathways of AMF in human pancreatic cancer cell lines.Results: Overexpression of AMF stimulated in vitro invasion of MIA PaCa-2 cells. In vivo, after orthotopic implantation into the pancreas of nude mice, parental and empty vector-transfected MIA PaCa-2 cells produced locally relatively small tumors with no evidence of liver metastasis, whereas AMF-transfected MIA PaCa-2 cells produced the large tumors and liver metastases. In addition, over-expression of AMF leads to down-regulation of E-cadherin expression associated with the up-regulation of the zinc-finger transcription factor SNAIL expression.Conclusions: The data submitted here show that AMF expression significantly contributes to the aggressive phenotype of human pancreatic cancer and thus may provide a novel prognostic and therapeutic target.

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Section: Introductionmentioning

confidence: 99%

Autocrine Motility Factor Signaling Enhances Pancreatic Cancer Metastasis

Tsutsumi

Yanagawa

Shimura

et al. 2004

Clinical Cancer Research

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“…3,4 We purified AMF from conditioned medium of murine metastatic fibrosarcoma, and demonstrated that AMF is identical to phosphohexose isomerase (PHI), also designated as glucose-6-phosphate isomerase (GPI), which is a ubiquitous enzyme catalyzing the conversion of glucose-6-phosphate to fructose-6-phosphate. 5 AMF/PHI has also been found to be identical to neuroleukin (NLK), 6,7 a neurotrophic growth factor that supports the survival of spinal and sensory neurons, 8 and maturation factor (MF) mediating the differentiation of human myeloid leukemic HL-60 cells to terminal monocytic cells, 9 suggesting that this cytokine is multifunctional, probably dependent on the target cells. AMF/PHI activities have shown to be elevated in the serum or urine of patients with disseminated malignant tumors such as gastrointestinal, kidney, breast, colorectal, and lung carcinomas, 10,11 , thereby being useful as a tumor-dissemination marker.…”

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confidence: 99%

Overexpression of autocrine motility factor in metastatic tumor cells: possible association with augmented expression of KIF3A and GDI-β

Yanagawa

Watanabe

Takeuchi

et al. 2004

Laboratory Investigation

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Autocrine motility factor (AMF), which is identical to phosphohexose isomerase (PHI)/glucose-6-phosphate isomerase (GPI) , a ubiquitous enzyme essential for glycolysis, neuroleukin (NLK), a neurotrophic growth factor, and maturation factor (MF) mediating the differentiation of human myeloid cells, enhances the motility and metastatic ability of tumor cells. AMF/PHI activity is elevated in the serum or urine in patients with malignant tumors. Here, we constructed an amf/phi/nlk/mf gene using adenovirus vector and transfected into two tumor cell lines. Overexpression of AMF/PHI/NLK/MF enhanced AMF secretion into the culture media in both tumor cell lines. However, upregulation of motility and metastatic ability was found only in metastatic fibrosarcoma cells expressing an AMF receptor, gp78, and was not found in gp78-undetectable osteosarcoma cells. Thus, not only serum AMF activity but also gp78-expression in tumor cells may be required for metastasis-related motility induction. With the use of microarray analyses, we detected two augmented genes, rho GDP dissociation inhibitor beta and kinesin motor 3A, as well as AMF itself. The RNA message and protein expression of these two molecules was confirmed to be upregulated, suggesting a possible association with AMF-induced signaling for cell motility and metastasis.

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“…This central role in the metabolism of phosphorylated sugars explains the strong impact of PGI deficiency in humans (6,7), as well as the interest as a therapeutic target in parasite metabolism (8). The PGI polypeptide chain, or perhaps a variation thereof, also has extracellular roles as neuroleukin, autocrine motility factor, and differentiation and maturation mediator (9)(10)(11)(12). These proteins promote antibody secretion by mononuclear cells, tumor cell motility, and differentiation of leukemia cells and a promyelocytic cell line (HL-60 cells), respectively.…”

mentioning

confidence: 99%

The crystal structure of rabbit phosphoglucose isomerase complexed with 5-phospho- d -arabinonohydroxamic acid

Arsenieva

Hardré

Salmon

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Phosphoglucose isomerase (EC 5.3.1.9) catalyzes the second step in glycolysis, the reversible isomerization of D-glucose 6-phosphate to D-fructose 6-phosphate. The reaction mechanism involves acid-base catalysis with proton transfer and proceeds through a cis-enediol(ate) intermediate. 5-Phospho-D-arabinonohydroxamic acid (5PAH) is a synthetic small molecule that resembles the reaction intermediate, differing only in that it has a nitrogen atom in place of C1. Hence, 5PAH is the best inhibitor of the isomerization reaction reported to date with a Ki of 2 ؋ 10 ؊7 M. Here we report the crystal structure of rabbit phosphoglucose isomerase complexed with 5PAH at 1.9 Å resolution. The interaction of 5PAH with amino acid residues in the enzyme active site supports a model of the catalytic mechanism in which Glu-357 transfers a proton between C1 and C2 and Arg-272 helps stabilize the intermediate. It also suggests a mechanism for proton transfer between O1 and O2. P hosphoglucose isomerase (PGI; EC 5.3.1.9) is a cytosolic glycolytic enzyme that catalyzes the reversible isomerization of D-glucose 6-phosphate (G6P) to D-fructose 6-phosphate (F6P). In addition to isomerase activity, PGI has been shown to display anomerase activity between pyranose anomers of G6P (1), between furanose anomers of F6P (2), and between those of D-mannose 6-phosphate (3), as well as C-2-epimerase activity on G6P (4). It also has roles in protein glycosylation, gluconeogenesis, and the pentose phosphate pathway (5). This central role in the metabolism of phosphorylated sugars explains the strong impact of PGI deficiency in humans (6, 7), as well as the interest as a therapeutic target in parasite metabolism (8). The PGI polypeptide chain, or perhaps a variation thereof, also has extracellular roles as neuroleukin, autocrine motility factor, and differentiation and maturation mediator (9-12). These proteins promote antibody secretion by mononuclear cells, tumor cell motility, and differentiation of leukemia cells and a promyelocytic cell line (HL-60 cells), respectively. More recently, PGI has also been identified as the antigen involved in rheumatoid arthritis of a mouse line (13), as a specific inhibitor toward myofibril-bound serine proteinase (14), and as the surface antigen involved in sperm agglutination (15). Because very little is known about how PGI is precisely involved in these various biological processes, this moonlighting protein (16) has been the subject of intense investigations.Biochemical characterization of PGI began over 50 years ago and includes inhibitor studies (1,(17)(18)(19)(20)(21)(22)(23)(24)(25), labeling studies (26-32), solvent exchange (33, 34), mutagenesis (35,36), and pH profile studies (20,37). A proposed multistep catalytic mechanism includes a ring-opening step followed by an isomerization step. The isomerization step proceeds via general acid-base catalysis with proton transfer. In the G6P to F6P direction, abstraction of the proton from C2 by an active site amino acid residue yields a 1,2-cis-enediol(ate) in...

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The neurotrophic factor neuroleukin is 90% homologous with phosphohexose isomerase

Cited by 258 publications

References 9 publications

Autocrine Motility Factor Signaling Enhances Pancreatic Cancer Metastasis

Autocrine Motility Factor Signaling Enhances Pancreatic Cancer Metastasis

Overexpression of autocrine motility factor in metastatic tumor cells: possible association with augmented expression of KIF3A and GDI-β

The crystal structure of rabbit phosphoglucose isomerase complexed with 5-phospho- d -arabinonohydroxamic acid

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