PMID- 7957666
OWN - NLM
STAT- MEDLINE
DCOM- 19941202
LR  - 20141120
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 215
IP  - 1
DP  - 1994 Nov
TI  - Gene expression of monocyte chemoattractant protein-1 in human monocytes is 
      regulated by cell density through protein tyrosine kinase and protein kinase C.
PG  - 172-9
AB  - 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.
FAU - Zen, K
AU  - Zen K
AD  - National Cardiovascular Center Research Institute, Osaka, Japan.
FAU - Masuda, J
AU  - Masuda J
FAU - Sasaguri, T
AU  - Sasaguri T
FAU - Kosaka, C
AU  - Kosaka C
FAU - Ogata, J
AU  - Ogata J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Benzoquinones)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemotactic Factors)
RN  - 0 (Cytokines)
RN  - 0 (Isoflavones)
RN  - 0 (Isoquinolines)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (Piperazines)
RN  - 0 (Quinones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sulfonamides)
RN  - 1W306TDA6S (Rifabutin)
RN  - 3WHH0066W5 (Vanadates)
RN  - 70563-58-5 (herbimycin)
RN  - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine)
RN  - 91742-10-8 (N-(2-guanidinoethyl)-5-isoquinolinesulfonamide)
RN  - DH2M523P0H (Genistein)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
MH  - Benzoquinones
MH  - Blotting, Northern
MH  - Cell Division
MH  - Cell Nucleus/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2
MH  - Chemotactic Factors/*biosynthesis/blood
MH  - Cytokines/*biosynthesis
MH  - *Gene Expression Regulation/drug effects
MH  - Genistein
MH  - Humans
MH  - Isoflavones/pharmacology
MH  - Isoquinolines/pharmacology
MH  - Lactams, Macrocyclic
MH  - Monocytes/cytology/drug effects/*metabolism
MH  - Piperazines/pharmacology
MH  - Protein Kinase C/antagonists & inhibitors/*blood
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/*blood
MH  - Quinones/pharmacology
MH  - RNA, Messenger/analysis/biosynthesis/blood
MH  - Rifabutin/analogs & derivatives
MH  - *Sulfonamides
MH  - Transcription, Genetic
MH  - Vanadates/pharmacology
EDAT- 1994/11/01 00:00
MHDA- 1994/11/01 00:01
CRDT- 1994/11/01 00:00
PHST- 1994/11/01 00:00 [pubmed]
PHST- 1994/11/01 00:01 [medline]
PHST- 1994/11/01 00:00 [entrez]
AID - S0014-4827(84)71329-2 [pii]
AID - 10.1006/excr.1994.1329 [doi]
PST - ppublish
SO  - Exp Cell Res. 1994 Nov;215(1):172-9. doi: 10.1006/excr.1994.1329.