Crystallization of a 2:2 complex of granulocyte-colony stimulating factor (GCSF) with the ligand-binding region of the GCSF receptor

Honjo, Eijiro; Tamada, Taro; Maeda, Yoshitake; Koshiba, Takumi; Matsukura, Yasuko; Okamoto, Tamotsu; Ishibashi, Matsujiro; Tokunaga, Masao; Kuroki, Ryota

doi:10.1107/s1744309105023080

Cited by 6 publications

(4 citation statements)

References 14 publications

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“…Protein preparation and crystallization of hGCSF and Ig-CRH domains of hGCSF-R were performed as described in ref. 21. Briefly, crystals were grown at 293 K in hanging drops using 1.5 mg͞ml protein solution over 0.2 M ammonium phosphate, and were identified as space group P3 2 21 with unit-cell parameters a ϭ b ϭ 134.8, c ϭ 105.7 Å.…”

Section: Methodsmentioning

confidence: 99%

Homodimeric cross-over structure of the human granulocyte colony-stimulating factor (GCSF) receptor signaling complex

Tamada

Honjo²,

Maeda³

et al. 2006

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

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117

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A crystal structure of the signaling complex between human granulocyte colony-stimulating factor (GCSF) and a ligand binding region of GCSF receptor (GCSF-R), has been determined to 2.8 Å resolution. The GCSF:GCSF-R complex formed a 2:2 stoichiometry by means of a cross-over interaction between the Ig-like domains of GCSF-R and GCSF. The conformation of the complex is quite different from that between human GCSF and the cytokine receptor homologous domain of mouse GCSF-R, but similar to that of the IL-6͞gp130 signaling complex. The Ig-like domain cross-over structure necessary for GCSF-R activation is consistent with previously reported thermodynamic and mutational analyses.ligand-receptor interaction ͉ x-ray crystallography ͉ IL-6 ͉ gp130

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Section: Methodsmentioning

confidence: 99%

Homodimeric cross-over structure of the human granulocyte colony-stimulating factor (GCSF) receptor signaling complex

Tamada

Honjo²,

Maeda³

et al. 2006

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

Self Cite

117

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“…It is an O-glycosylated protein with 174 residues composed of a 4--helical bundle, similar to the folding of INF [48]. Recombinant G-CSF (filgrastim, rhG-CSF) produced in E. coli is indicated for the treatment of neutropenia to increase circulating neutrophils.…”

Section: Granulocyte Colony Stimulating Factormentioning

confidence: 99%

Recombinant Human Serum Albumin Fusion Proteins and Novel Applications in Drug Delivery and Therapy

Rogers¹,

Dong²,

Li³

et al. 2015

CPD

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Fusion proteins have been well-studied and widely applied in biopharmaceutics. Albumin fusion proteins are simple to construct, easy to purify, and stable to formulate. One main application of fusion protein is to extend the plasma half-life of therapeutic proteins and peptides. Albiglutide for diabetes treatment is the first albumin fusion protein drug approved by FDA. Balugrastim and other albumin fusion proteins have been evaluated in clinical trials. Taking advantage of the physiological functions of albumin, albumin fusion proteins can also been applied to act on an essential intracellular target and carry fatty acid-modified drugs. This novel approach makes it possible to co-deliver two different types of drug to one tumor cell for synergistic cytotoxicity.

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“…Neutrophils up-regulate their levels of GCSFR as they differentiate from progenitor cell to mature neutrophil, with 50-500 GCSF receptors per cell [278]. Structural analysis showed GCSF forms a homodimer, binds two GCSFRs, and leads to receptor homodimerization in a 2:2 complex [279][280][281]. Binding of a homodimeric GCSF to two GCSF receptors triggers intracellular signaling through the JAK/STAT, Ras/Raf/Erk, or PI3K pathways [275,277,282].…”

Section: Granulocyte Colony-stimulating Factor Receptormentioning

confidence: 99%

Regulation of Teleost Macrophage and Neutrophil Cell Development by Growth Factors and Transcription Factors

Katzenback¹,

Katakura²,

Belosevic³

2012

New Advances and Contributions to Fish Biology

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Additional information is available at the end of the chapter http://dx.doi.org/10.5772/53589 . IntroductionMacrophages and neutrophils are the sentinel cells of the innate immune response of vertebrates, such as bony fish teleosts . "s phagocytic myeloid cells, they are involved in homeostatic mechanisms, wound healing, and the detection, elimination and clearance of foreign entities including tumors, virus-infected cells and invading pathogens. Furthermore, macrophages and neutrophils are responsible for producing hundreds of bioactive molecules that are important in pathogen recognition and destruction, cellular communication and activation, initiation of an adaptive immune response and later, resolution of an inflammatory response and tissue repair. Neutrophils and macrophages, while essential to survival, have a finite lifespan. Therefore, a manufacturing centre, the hematopoietic niche, is needed for the production of myeloid cells. The hematopoietic niche must maintain basal myeloid cell production levels during homeostasis, yet retain the flexibility to ramp-up cell production in response to physiological demands, such as pathogenic insult. The development of macrophages monopoiesis and neutrophils granulopoiesis is collectively known as myelopoiesis, and is regulated by the complex interaction of colony-stimulating factors CSFs , their receptors, and intracellular transcription factor machinery that control lineage fate decisions and terminal differentiation events.Over the past years, research using the mouse model system has culminated in the identification of the site s of myelopoiesis, the progenitor cell types that give rise to mature myeloid cells, the extracellular and intracellular cues required, and a detailed understanding of the complex intracellular and extracellular milieu of factors that drive this tightly controlled © 2013 Katzenback et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.process. From these studies we understand hematopoiesis as an exquisitely fine-tuned, highly regulated, process whereby all blood cells develop from a small number of hematopoietic stem cells HSCs . HSCs are characterized as long-term repopulating, pluripotent, quiescent cells that undergo symmetrical self-renewal to sustain the population of HSCs within the hematopoietic niche, or asymmetrical division to give rise to hematopoietic progenitor cells HPCs [ ]. HPCs can develop along the lymphoid lineage, termed lymphopoiesis, to give rise to "-cells, T-cells, natural killer NK cells and dendritic cells DCs . "lternatively, HPCs can develop along an erythroid lineage, termed erythropoiesis, to give rise to erythrocytes and megakaryocytes, or develop along a myeloid lineage to give rise to granulocytes neutrophils, basophils, eosinophils, mast cells , mononuclear phagoc...

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Crystallization of a 2:2 complex of granulocyte-colony stimulating factor (GCSF) with the ligand-binding region of the GCSF receptor

Cited by 6 publications

References 14 publications

Homodimeric cross-over structure of the human granulocyte colony-stimulating factor (GCSF) receptor signaling complex

Homodimeric cross-over structure of the human granulocyte colony-stimulating factor (GCSF) receptor signaling complex

Recombinant Human Serum Albumin Fusion Proteins and Novel Applications in Drug Delivery and Therapy

Regulation of Teleost Macrophage and Neutrophil Cell Development by Growth Factors and Transcription Factors

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