Hematopoietic Activity of Granulocyte/macrophage Colony-stimulating Factor is Dependent Upon Two Distinct Regions of the Molecule: Functional Analysis Based Upon the Activities of Interspecies Hybrid Growth Factors

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1989 Feb 1

PMID 2645577

Citations 15

Authors

K Kaushansky

S G Shoemaker

S Alfaro

C Brown

Affiliations

Soon will be listed here.

Abstract

Granulocyte/macrophage colony-stimulating factor (GM-CSF) is an acidic glycoprotein that stimulates hematopoiesis in vitro and in vivo. Despite a high degree of sequence homology, the GM-CSFs from human and murine sources fail to crossreact in their respective colony-forming assays. On the basis of this finding, a series of hybrid molecules containing various proportions of human- and murine-specific amino acid sequences were generated by recombinant DNA techniques and assayed for species-specific activity against human and murine marrow target cells. Two regions of GM-CSF, residues 38-48 and residues 95-111, were found to be critical for hematopoietic function. These regions are structurally characterized by an amphiphilic helix and by a disulfide-bonded loop, respectively, and are homologous in position in the human and murine growth factors. In addition, competition assays suggested that, together, these regions bind to the GM-CSF receptor.

Citing Articles

Thrombopoietin, the Primary Regulator of Platelet Production: From Mythos to Logos, a Thirty-Year Journey.

Kaushansky K Biomolecules. 2024; 14(4).

PMID: 38672505 PMC: 11047867. DOI: 10.3390/biom14040489.

Recombinant Newcastle Disease Virus Immunotherapy Drives Oncolytic Effects and Durable Systemic Antitumor Immunity.

Harper J, Burke S, Travers J, Rath N, Leinster A, Navarro C Mol Cancer Ther. 2021; 20(9):1723-1734.

PMID: 34224361 PMC: 9398146. DOI: 10.1158/1535-7163.MCT-20-0902.

Recombinant Granulocyte-Macrophage Colony-Stimulating Factor (rGM-CSF) : A Review of its Pharmacological Properties and Prospective Role in the Management of Myelosuppression.

Grant S, Heel R Drugs. 2017; 43(4):516-560.

PMID: 28421558 DOI: 10.2165/00003495-199243040-00008.

Delivery of GM-CSF to Protect against Influenza Pneumonia.

Subramaniam R, Hillberry Z, Chen H, Feng Y, Fletcher K, Neuenschwander P PLoS One. 2015; 10(4):e0124593.

PMID: 25923215 PMC: 4414562. DOI: 10.1371/journal.pone.0124593.

Glycosylation, disulfide bond formation, and the presence of a WSXWS-like motif in the orf virus GIF protein are critical for maintaining the integrity of Binding to ovine granulocyte-macrophage colony-stimulating factor and interleukin-2.

McInnes C, Deane D, Haig D, Percival A, Thomson J, Wood A J Virol. 2005; 79(17):11205-13.

PMID: 16103172 PMC: 1193636. DOI: 10.1128/JVI.79.17.11205-11213.2005.

References

Gough N, Metcalf D, Gough J, Grail D, Dunn A . Structure and expression of the mRNA for murine granulocyte-macrophage colony stimulating factor. EMBO J. 1985; 4(3):645-53. PMC: 554237. DOI: 10.1002/j.1460-2075.1985.tb03678.x. View

Wong G, Witek J, Temple P, Wilkens K, Leary A, Luxenberg D . Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985; 228(4701):810-5. DOI: 10.1126/science.3923623. View

Miyatake S, Otsuka T, Yokota T, Lee F, Arai K . Structure of the chromosomal gene for granulocyte-macrophage colony stimulating factor: comparison of the mouse and human genes. EMBO J. 1985; 4(10):2561-8. PMC: 554544. DOI: 10.1002/j.1460-2075.1985.tb03971.x. View

Metcalf D . The molecular biology and functions of the granulocyte-macrophage colony-stimulating factors. Blood. 1986; 67(2):257-67. View

Gasson J, Kaufman S, Weisbart R, Tomonaga M, Golde D . High-affinity binding of granulocyte-macrophage colony-stimulating factor to normal and leukemic human myeloid cells. Proc Natl Acad Sci U S A. 1986; 83(3):669-73. PMC: 322925. DOI: 10.1073/pnas.83.3.669. View

Karten M, Rivier J . Gonadotropin-releasing hormone analog design. Structure-function studies toward the development of agonists and antagonists: rationale and perspective. Endocr Rev. 1986; 7(1):44-66. DOI: 10.1210/edrv-7-1-44. View

Donahue R, Wang E, Stone D, Kamen R, Wong G, Sehgal P . Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF. Nature. 1986; 321(6073):872-5. DOI: 10.1038/321872a0. View

Meister A, Uze G, Mogensen K, GRESSER I, Tovey M, Grutter M . Biological activities and receptor binding of two human recombinant interferons and their hybrids. J Gen Virol. 1986; 67 ( Pt 8):1633-43. DOI: 10.1099/0022-1317-67-8-1633. View

Rosenblatt M . Peptide hormone antagonists that are effective in vivo. Lessons from parathyroid hormone. N Engl J Med. 1986; 315(16):1004-13. DOI: 10.1056/NEJM198610163151606. View

10.

Broudy V, Kaushansky K, Segal G, Harlan J, Adamson J . Tumor necrosis factor type alpha stimulates human endothelial cells to produce granulocyte/macrophage colony-stimulating factor. Proc Natl Acad Sci U S A. 1986; 83(19):7467-71. PMC: 386739. DOI: 10.1073/pnas.83.19.7467. View

11.

Weber H, Valenzuela D, Lujber G, Gubler M, Weissmann C . Single amino acid changes that render human IFN-alpha 2 biologically active on mouse cells. EMBO J. 1987; 6(3):591-8. PMC: 553438. DOI: 10.1002/j.1460-2075.1987.tb04795.x. View

12.

Clark S, Kamen R . The human hematopoietic colony-stimulating factors. Science. 1987; 236(4806):1229-37. DOI: 10.1126/science.3296190. View

13.

Groopman J, Mitsuyasu R, DeLeo M, Oette D, Golde D . Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med. 1987; 317(10):593-8. DOI: 10.1056/NEJM198709033171003. View

14.

Palaszynski E . Synthetic C-terminal peptide of IL-1 functions as a binding domain as well as an antagonist for the IL-1 receptor. Biochem Biophys Res Commun. 1987; 147(1):204-11. DOI: 10.1016/s0006-291x(87)80107-9. View

15.

Kaushansky K, OHara P, Hart C, Forstrom J, Hagen F . Role of carbohydrate in the function of human granulocyte-macrophage colony-stimulating factor. Biochemistry. 1987; 26(15):4861-7. DOI: 10.1021/bi00389a038. View

16.

Kaushansky K, Lin N, Adamson J . Interleukin 1 stimulates fibroblasts to synthesize granulocyte-macrophage and granulocyte colony-stimulating factors. Mechanism for the hematopoietic response to inflammation. J Clin Invest. 1988; 81(1):92-7. PMC: 442478. DOI: 10.1172/JCI113316. View

17.

Clark-Lewis I, Lopez A, To L, Vadas M, Schrader J, HOOD L . Structure-function studies of human granulocyte-macrophage colony-stimulating factor. Identification of residues required for activity. J Immunol. 1988; 141(3):881-9. View

18.

Kaushansky K, Broudy V, Harlan J, Adamson J . Tumor necrosis factor-alpha and tumor necrosis factor-beta (lymphotoxin) stimulate the production of granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, and IL-1 in vivo. J Immunol. 1988; 141(10):3410-5. View

19.

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

20.

Graham F, Van Der Eb A . A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973; 52(2):456-67. DOI: 10.1016/0042-6822(73)90341-3. View