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Gene expression of monocyte chemoattractant protein-1 in human monocytes is regulated by cell density through protein tyrosine kinase and protein kinase C.
Exp Cell Res. 1994 Nov; 215(1):172-9.EC

Abstract

The present study investigated the signal transduction pathways leading to the gene expression for monocyte chemoattractant protein-1 (MCP-1) in human monocytes. By Northern blot analysis, MCP-1 mRNA was undetectable in freshly isolated monocytes, but was induced and reached a maximal level at 4 h during culture. The level of accumulated mRNA altered with cell density of the monocytes and was highest at a density of 1 x 10(6) cells/ml. Nuclear run-on assay demonstrated that this cell density-dependent expression of MCP-1 mRNA was regulated at the transcriptional level, and protein tyrosine kinase (PTK) inhibitors, genistein and herbimycin A, completely abrogated this gene transcription. Immunoblot analysis for phosphotyrosine in whole cell lysates demonstrated gradual increases in tyrosine phosphorylation of 55-, 60-, and 70-kDa proteins during culture. Cell density regulated tyrosine phosphorylation of 70-kDa protein in parallel with alterations in MCP-1 mRNA expression. The protein kinase C (PKC) inhibitor H-7 also abrogated the gene transcription and suppressed tyrosine phosphorylation of 70-kDa protein, whereas HA1004, a structural analogue of H-7, did not. These results suggest that MCP-1 gene expression in cultured monocytes is regulated by the cell density at the transcriptional level and that the signaling pathways leading to the gene transcription are mediated through PTK and PKC. It is also suggested that PKC activity plays a critical role in tyrosine phosphorylation of 70-kDa protein, which may mediate signals regulating the cell density-dependent expression of the MCP-1 gene.

Authors+Show Affiliations

National Cardiovascular Center Research Institute, Osaka, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7957666

Citation

Zen, K, et al. "Gene Expression of Monocyte Chemoattractant Protein-1 in Human Monocytes Is Regulated By Cell Density Through Protein Tyrosine Kinase and Protein Kinase C." Experimental Cell Research, vol. 215, no. 1, 1994, pp. 172-9.
Zen K, Masuda J, Sasaguri T, et al. Gene expression of monocyte chemoattractant protein-1 in human monocytes is regulated by cell density through protein tyrosine kinase and protein kinase C. Exp Cell Res. 1994;215(1):172-9.
Zen, K., Masuda, J., Sasaguri, T., Kosaka, C., & Ogata, J. (1994). Gene expression of monocyte chemoattractant protein-1 in human monocytes is regulated by cell density through protein tyrosine kinase and protein kinase C. Experimental Cell Research, 215(1), 172-9.
Zen K, et al. Gene Expression of Monocyte Chemoattractant Protein-1 in Human Monocytes Is Regulated By Cell Density Through Protein Tyrosine Kinase and Protein Kinase C. Exp Cell Res. 1994;215(1):172-9. PubMed PMID: 7957666.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gene expression of monocyte chemoattractant protein-1 in human monocytes is regulated by cell density through protein tyrosine kinase and protein kinase C. AU - Zen,K, AU - Masuda,J, AU - Sasaguri,T, AU - Kosaka,C, AU - Ogata,J, PY - 1994/11/1/pubmed PY - 1994/11/1/medline PY - 1994/11/1/entrez SP - 172 EP - 9 JF - Experimental cell research JO - Exp Cell Res VL - 215 IS - 1 N2 - The present study investigated the signal transduction pathways leading to the gene expression for monocyte chemoattractant protein-1 (MCP-1) in human monocytes. By Northern blot analysis, MCP-1 mRNA was undetectable in freshly isolated monocytes, but was induced and reached a maximal level at 4 h during culture. The level of accumulated mRNA altered with cell density of the monocytes and was highest at a density of 1 x 10(6) cells/ml. Nuclear run-on assay demonstrated that this cell density-dependent expression of MCP-1 mRNA was regulated at the transcriptional level, and protein tyrosine kinase (PTK) inhibitors, genistein and herbimycin A, completely abrogated this gene transcription. Immunoblot analysis for phosphotyrosine in whole cell lysates demonstrated gradual increases in tyrosine phosphorylation of 55-, 60-, and 70-kDa proteins during culture. Cell density regulated tyrosine phosphorylation of 70-kDa protein in parallel with alterations in MCP-1 mRNA expression. The protein kinase C (PKC) inhibitor H-7 also abrogated the gene transcription and suppressed tyrosine phosphorylation of 70-kDa protein, whereas HA1004, a structural analogue of H-7, did not. These results suggest that MCP-1 gene expression in cultured monocytes is regulated by the cell density at the transcriptional level and that the signaling pathways leading to the gene transcription are mediated through PTK and PKC. It is also suggested that PKC activity plays a critical role in tyrosine phosphorylation of 70-kDa protein, which may mediate signals regulating the cell density-dependent expression of the MCP-1 gene. SN - 0014-4827 UR - https://www.unboundmedicine.com/medline/citation/7957666/Gene_expression_of_monocyte_chemoattractant_protein_1_in_human_monocytes_is_regulated_by_cell_density_through_protein_tyrosine_kinase_and_protein_kinase_C_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(84)71329-2 DB - PRIME DP - Unbound Medicine ER -