Why do hemopoietic growth factor receptors interact with each other?

doi:10.1016/0167-5699(87)90140-X

Immunology Today

Volume 8, Issue 5, 1987, Pages 134-140

Immunology Today

https://doi.org/10.1016/0167-5699(87)90140-X Get rights and content

Abstract

Hemopoietic growth factors (colony-stimulating factors, CSFs) interact with distinct cellular receptors that recognize only their cognate ligand. Yet, like other growth factor/receptor systems, the binding of one type of CSF to its receptor can ‘down-modulate’ the availability of a different tyoe of CSF receptor. In this article Nicos Nicola discusses the distinctive pattern of] CSF-receptor modulations and suggests a novel interpretation of such modulations as a means of coupling receptor-derived signals which is consistent with the known biology of the system.

References (44)

N.A. Nicola et al.
Immunol. Today
(1984)
D. Metcalf
Blood
(1986)
C.G. Begley et al.
Blood
(1986)
C.J. Morgan et al.
Biochem. Biophys. Res. Commun.
(1984)
C.J. Sherr et al.
Cell
(1985)
E.R. Stanley et al.
J. Immunol. Methods
(1981)
L.J. Guilbert et al.
J. Biol. Chem.
(1986)
N.A. Nicola et al.
J. Biol. Chem.
(1986)
L.S. Park et al.
J. Biol. Chem.
(1986)
L.S. Park et al.
J. Biol. Chem.
(1986)

R.K. Shadduck et al.

Blood

(1983)

R.K. Assoian

J. Biol. Chem.

(1985)

L.J. Guilbert et al.

J. Immunol. Methods

(1984)

F. Walker et al.

Cell

(1985)

T. Miyake et al.

J. Biol. Chem.

(1977)

D. Metcalf

Hemopoietic Colony Stimulating Factors

(1984)

D. Metcalf

Science

(1985)

M.A. Vadas et al.

Lymphokines

(1985)

D. Metcalf et al.

Int. J. Cancer

(1982)

C.W. Rettenmier et al.

J. Clin. Invest.

(1986)

R.M. Kris et al.

Biotechnology

(1985)

L.J. Guilbert et al.

J. Cell. Biol.

(1980)

Cited by (43)

Differential expression of granulocyte-macrophage colony-stimulating factor and IL-3 receptor subunits on human CD34<sup>+</sup> cells and leukemic cell lines
1995, The Journal of Allergy and Clinical Immunology
Cytokines transduce their signals through specific receptors. Receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, and IL-5 share the common signal transducing subunit (βc), whereas the α subunits function as specific ligand binding components. In this study we prepared specific mouse monoclonal antibodies against human GM-CSF receptor-α subunit (hGMRα) by immunizing mice with Ba/F3 cells transfected with hGMRα complementary DNA. Using these anti-hGMRα antibodies in combination with antibodies against IL-3 receptor-α (IL-3Rα), βc subunits, and c-kit, we examined expression patterns and modulation of these receptor subunits on several human hematopoietic cells, including CD34⁺ cells and leukemic cell lines. GMRα and IL-3Rα were expressed on GM-CSF- and IL-3-responsive cell lines, such as TF-1 and UT-7, whereas the expression levels were much lower on UT-7E, a GM-CSF- and IL-3-unresponsive subline of UT-7. The GMRα subunit was expressed only on mature granulocytes and monocytes, and IL-3Rα was expressed on monocytes but not on mature granulocytes, and none of these subunits were expressed on lymphocytes. For CD34⁺ cells, GMRα was expressed more abundantly on CD34⁺CD33^high cells than on CD34⁺CD33^low cells, whereas IL-3Rα was expressed more abundantly on CD34⁺CD33^low cells than on CD34⁺CD33^high and CD34⁺CD33^neg cells. Slight but significant expression of the βc subunit was detected on CD34⁺ cells. Expression of not only GMRα and IL-3Rα subunits but also c-kit was specifically downregulated by 48-hour incubation with their respective ligands. Receptor transmodulation between GM-CSF, IL-3, and stem cell factor (or kit ligand) was not detected on CD34⁺ cells in 48-hour cultures. We also detected upregulation of these α subunits by IL-1α and interferon-γ on leukemic cell lines. Our study showed expression levels for each receptor subunit—including GMR, IL-3R, and c-kit on human bone marrow and peripheral blood cells and leukemic cell lines—and revealed differential regulation of the expression of the receptor subunits. (J ALLERGY CLIN IMMUNOL 1995;96:1083-99.)
Signal Transduction by the Colony-Stimulating Factor-1 Receptor; Comparison to Other Receptor Tyrosine Kinases
1992, Current Topics in Cellular Regulation
The colony-stimulating factor-1 (CSF-1) receptor (CSF-1R), encoded by the protooncogene c-fms, is the cell surface receptor for the macrophage colony-stimulating factor. It is a member of the tyrosine kinase family of growth factor receptors, which are believed to exert their biological influence through the catalysis of tyrosine phosphorylation of key intracellular substrates. In addition, CSF-1R is a hematopoietic growth factor receptor and its expression is lineage-specific, being confined to monocytes and macrophages and their bone marrow progenitors. It has been found on placental trophoblasts. This chapter discusses the signaling mechanisms utilized by CSF-1R and the similarities and differences when compared to other receptor tyrosine kinases. It discusses the mechanism of ligand-induced kinase activation and the potential biological role of the few intracellular substrates so far identified. What is known to date regarding the biochemical aspects of the function of CSF-1R provides one with only the beginning of an understanding of the biological aspects of its function, that is, its essential role in the proliferation, differentiation, and survival of monocytes and macrophages. As more knowledge is accumulated concerning the different components of the intracellular signaling pathways, this gap is certain to be filled in.
Subunit promiscuity among hemopoietic growth factor receptors
1991, Cell
Expression of the GM-CSF gene after retroviral transfer in hematopoietic stem cell lines induces synchronous granulocyte-macrophage differentiation
1991, Cell
Multipotent murine stem cell lines (FDC-Pmix) depend on IL-3 for self-renewal and proliferation and can be induced to differentiate into multiple hematopoietic lineages. Single FDC-Pmix cells infected with retroviral vectors expressing GM-CSF are induced to differentiate into granulocytes and macrophages. This results in a complete loss of clonogenic cells if IL-3 is not exogenously supplied; however, multipotent variants can be selected that do not terminally differentiate if cells are kept in the presence of IL-3. Unidirectional and synchronous granulocyte and macrophage differentiation accompanied with loss of self-renewal capacity is induced when IL-3 is removed. Our data indicate that activation of the GM-CSF receptor induces differentiation of stem cells by an instructive mechanism that can be blocked by the activated IL-3 receptor. A model of how receptors can induce proliferation and cell-specific differentiation by two separate pathways is discussed.
Haemopoietic growth factors: Unravelling the secrets of blood formation
1991, European Journal of Cancer and Clinical Oncology
Evidence for an epidermal cytokine network
1990, Journal of Investigative Dermatology
Cytokines are (glyco)proteins that are synthesized and secreted by various cells, which bind to specific receptors on target cells and which regulate activation, proliferation, and differentiation of immune as well as non-immune cells. Keratinocytes upon injury release interleukin (IL)-1, IL-6, IL-8, colony-stimulating factors, and tumor-necrosis factor, as well as growth and suppressor factors. There is also strong evidence for a network of interacting cytokines, which has been only partially characterized so far, maintaining a proper balance. However, excessive or insufficient production of these mediators may contribute to certain disease states, particularly those with infectious and autoimmune genesis. Therefore the understanding of cytokine interactions may be helpful in elucidating the pathomechanisms of such diseases. Moreover, certain cytokines, as well as their analogues and antagonists, may prove to be of therapeutic value.

View all citing articles on Scopus

View full text

Why do hemopoietic growth factor receptors interact with each other?

Abstract

Immunol. Today

Blood

Blood

Biochem. Biophys. Res. Commun.

Cell

J. Immunol. Methods

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Blood

J. Biol. Chem.

J. Immunol. Methods

Cell

J. Biol. Chem.

Hemopoietic Colony Stimulating Factors

Science

Lymphokines

Int. J. Cancer

J. Clin. Invest.

Biotechnology

J. Cell. Biol.