scholarly journals Ligand-independent Cell Surface Expression of the Human Soluble Granulocyte-Macrophage Colony-stimulating Factor Receptor α Subunit Depends on Co-expression of the Membrane-associated Receptor β Subunit

1996 ◽  
Vol 271 (26) ◽  
pp. 15330-15335 ◽  
Author(s):  
Elizabeth W. Murray ◽  
Carin Pihl ◽  
Annette Morcos ◽  
Christopher B. Brown
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Β Subunit ◽  
Colony Stimulating Factor ◽  
Α Subunit ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals Coupling of Osteopontin and Its Cell Surface Receptor CD44 to the Cell Survival Response Elicited by Interleukin-3 or Granulocyte-Macrophage Colony-Stimulating Factor

2000 ◽  
Vol 20 (8) ◽  
pp. 2734-2742 ◽  
Author(s):  
Yi-Hung Lin ◽  
Chang-Jen Huang ◽  
Jyh-Rong Chao ◽  
Shui-Tsung Chen ◽  
Shern-Fwu Lee ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Surface Receptor ◽  
Β Subunit ◽  
Colony Stimulating Factor ◽  
Adhesion Protein ◽  
Gm Csf ◽  
Surface Receptor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

ABSTRACT The receptors for interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) share a common β subunit, the distal cytoplasmic domain of which is essential for the promotion of cell survival by these two cytokines. Genes whose expression is specifically induced by signaling through the distal cytoplasmic domain of this receptor β subunit were screened by a subtraction cloning approach in derivatives of a mouse pro-B-cell line. One gene thus identified was shown to encode a protein highly homologous (with only 7 amino acid substitutions) to murine osteopontin (OPN), a secreted adhesion protein. Conditioned medium from cells expressing wild-type OPN, but not that from cells expressing a deletion mutant lacking residues 79 to 140, increased the viability of a non-OPN-producing cell line in the presence of human GM-CSF. Antibody blocking experiments revealed that OPN produced as a result of IL-3 or GM-CSF signaling was secreted into the medium and, through binding to its cell surface receptor, CD44, contributed to the survival-promoting activities of these two cytokines. Furthermore, coupling of the OPN-CD44 pathway to the survival response to IL-3 was also demonstrated in primary IL-3-dependent mouse bone marrow cells. These results thus show that induction of an extracellular adhesion protein and consequent activation of its cell surface receptor are important for the antiapoptotic activities of IL-3 and GM-CSF.

scholarly journals Expression of Granulocyte-Macrophage Colony-Stimulating Factor Receptors in Human Prostate Cancer

Blood ◽  
1998 ◽  
Vol 91 (3) ◽  
pp. 1037-1043 ◽  
Author(s):  
Coralia I. Rivas ◽  
Juan Carlos Vera ◽  
Fernando Delgado-López ◽  
Mark L. Heaney ◽  
Victor H. Guaiquil ◽  
...  
Keyword(s):  
Human Prostate ◽  
Β Subunit ◽  
Colony Stimulating Factor ◽  
Lncap Cells ◽  
Α Subunit ◽  
Gm Csf ◽  
High Affinity ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

We studied the expression and function of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor in the human prostate carcinoma cell line LNCaP and looked for its presence in normal and neoplastic human prostatic tissue. The GM-CSF receptor is composed of two subunits, α and β. While the isolated α subunit binds GM-CSF at low-affinity, the isolated β subunit does not bind GM-CSF by itself; but complexes with the α subunit to form a high-affinity receptor. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) showed expression of mRNAs encoding the α and β subunits of the GM-CSF receptor in LNCaP cells, and the presence of the α and β proteins was confirmed by immunolocalization with anti-α and anti-β antibodies. Receptor binding studies using radiolabeled GM-CSF showed that LNCaP cells have about 150 high-affinity sites with a kd of 40 pmol/L and approximately 750 low-affinity sites with a kd of 2 nmol/L. GM-CSF signaled, in a time- and dose-dependent manner, for protein tyrosine phosphorylation and induced the proliferation of the LNCaP cells. Immunolocalization studies showed low level expression of GM-CSF α and β subunits in normal prostate tissue, with substantial expression in benign prostatic hyperplasia and prominent expression in neoplastic prostate tissue. Maximal expression of both subunits was observed in prostatic carcinomas metastatic to lymph node and bone. Tumor cells that stained positively with anti-α subunit antibodies were also reactive with anti-β subunit antibodies, indicating that they express high-affinity GM-CSF receptors. Our data show that the LNCaP cells express functional GM-CSF receptors and that prostatic carcinomas have prominent GM-CSF receptor expression. These findings imply that both hyperplastic and neoplastic prostatic tissues may be responsive to GM-CSF.

scholarly journals Expression of Granulocyte-Macrophage Colony-Stimulating Factor Receptors in Human Prostate Cancer

Blood ◽  
1998 ◽  
Vol 91 (3) ◽  
pp. 1037-1043 ◽  
Author(s):  
Coralia I. Rivas ◽  
Juan Carlos Vera ◽  
Fernando Delgado-López ◽  
Mark L. Heaney ◽  
Victor H. Guaiquil ◽  
...  
Keyword(s):  
Human Prostate ◽  
Β Subunit ◽  
Colony Stimulating Factor ◽  
Lncap Cells ◽  
Α Subunit ◽  
Gm Csf ◽  
High Affinity ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract We studied the expression and function of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor in the human prostate carcinoma cell line LNCaP and looked for its presence in normal and neoplastic human prostatic tissue. The GM-CSF receptor is composed of two subunits, α and β. While the isolated α subunit binds GM-CSF at low-affinity, the isolated β subunit does not bind GM-CSF by itself; but complexes with the α subunit to form a high-affinity receptor. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) showed expression of mRNAs encoding the α and β subunits of the GM-CSF receptor in LNCaP cells, and the presence of the α and β proteins was confirmed by immunolocalization with anti-α and anti-β antibodies. Receptor binding studies using radiolabeled GM-CSF showed that LNCaP cells have about 150 high-affinity sites with a kd of 40 pmol/L and approximately 750 low-affinity sites with a kd of 2 nmol/L. GM-CSF signaled, in a time- and dose-dependent manner, for protein tyrosine phosphorylation and induced the proliferation of the LNCaP cells. Immunolocalization studies showed low level expression of GM-CSF α and β subunits in normal prostate tissue, with substantial expression in benign prostatic hyperplasia and prominent expression in neoplastic prostate tissue. Maximal expression of both subunits was observed in prostatic carcinomas metastatic to lymph node and bone. Tumor cells that stained positively with anti-α subunit antibodies were also reactive with anti-β subunit antibodies, indicating that they express high-affinity GM-CSF receptors. Our data show that the LNCaP cells express functional GM-CSF receptors and that prostatic carcinomas have prominent GM-CSF receptor expression. These findings imply that both hyperplastic and neoplastic prostatic tissues may be responsive to GM-CSF.

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