Browse > Article

PMA Activates Stat3 in the Jak/Stat Pathway and Induces SOCS5 in Rat Brain Astrocytes  

Hwang, Mi-Na (Research Institute, National Cancer Center)
Kim, Kwang Soo (Department of Pharmacology, Ajou University School of Medicine)
Choi, Yo-Woo (Research Institute, National Cancer Center)
Jou, Ilo (Department of Pharmacology, Ajou University School of Medicine)
Yoon, Sungpil (Research Institute, National Cancer Center)
Abstract
Suppressors of cytokine signaling (SOCS) family members are negative feedback regulators of the Jak/Stat pathway, which is an essential inflammatory signaling pathway. We investigated expression of eight members of the SOCS family in rat astrocytes, using two inflammatory stimulants, PMA and IFN-${\gamma}$. Only a few SOCS genes were induced by both stimulants, and we detected an increase in SOCS5 protein with PMA. PMA activated the Jnk, Erk, p38, and Jak/Stat signal pathways. In addition, it increased the level of activated-Stat3 resulting from tyrosine phosphorylation. A gel-shift assay showed that a protein in nuclear extracts from PMA-treated cells was able to bind to Stat binding elements. These results suggest that activated Stat3 binds to SOCS promoters and leads to their transcriptional induction.
Keywords
Astrocyte; IFN-${\gamma}$; Jak/Stat; PMA; SOCS; Stat3;
Citations & Related Records

Times Cited By Web Of Science : 9  (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Darnell, J. E. Jr., Kerr, I. M., and Stark, G. R. (1994) Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264, 1415− 1421
2 Frohman, E. M., Frohman, T. C., Dustin, M. L., Vayuvegula, B., Choi, B., et al. (1989) The induction of intercellular adhesion molecule 1 (ICAM-1) expression on human fetal astrocytes by interferon-gamma, tumor necrosis factor alpha, lymphotoxin, and interleukin-1: relevance to interacerabral antigen presentation. J. Neuroimmunol. 23, 117−124
3 Igaz, P., Toth, S., and Falus, A. (2001) Biological and clinical significance of the JAK-STAT pathway; lessons from knockout mice. Inflamm. Res. 50, 435−441
4 Kishimoto, T., Taga, T., and Akira S. (1994) Cytokine signal transduction. Cell 76, 253−262
5 Streit, W. J., Walter, S. A., and Pennell, N. A. (1999) Reactive microgliosis. Prog. Neurobiol. 57, 563−581
6 Wen, Z., Zhong, Z., and Darnell, J. E. Jr. (1995) Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell 82, 241−250
7 Zhou, Z. H., Chaturvedi, P., Han, Y. L., Aras, S., Li, Y. S., et al. (1998) IFN-gamma induction of the human monocyte chemoattractant protein (hMCP)-1 gene in astrocytoma cells: functional interaction between an IFN-gamma-activated site and a GC-rich element. J. Immunol. 160, 3908−3916
8 Aeder, S. E., Martin, P. M., Soh, J. W., and Hussaini, I. M. (2004) PKC-eta mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways. Oncogene 23, 9062−9069
9 Reid, G. A. and Schatz, G. (1982) Import of proteins into mitochondria. Extramitochondrial pools and post-translational import of mitochondrial protein precursors in vivo. J. Biol. Chem. 257, 13062−13067
10 Yang, M. S., Lee, J., Ji, K. A., Min, K. J., Lee, M. A., et al. (2004) Thrombin induces suppressor of cytokine signaling 3 expression in brain microglia via protein kinase Cdelta activation. Biochem. Biophys. Res. Commun. 317, 811−816
11 Vitkovic, L., Aloyo, V. J., Maeda, S., Benzil, D. L., Bressler, J. P., et al. (2005) Identification of myristorylated alanine-rich C kinase substrate (MARCKS) in astrocytes. Front. Biosci. 10, 160−165
12 Hilton, D. J., Richardson, R. T., Alexander, W. S., Viney, E. M., Willson, T. A., et al. (1998) Twenty proteins containing a Cterminal SOCS box form five structural classes. Proc. Natl. Acad. Sci. USA 95, 114−119
13 Vanguri, P. (1995) Interferon-gamma-inducible genes in primary glial cells of the central nervous system: comparisons of astrocytes with microglia and Lewis with brown Norway rats. J. Neuroimmunol. 56, 35−43
14 Jeon, S. B., Ji, K. A., You, H. J., Kim, J. H., Jou, I., et al. (2005) Nordihydroguariaretic acid inhibits IFN-gamma-induced STAT tyrosine phosphorylation in rat brain astrocytes. Biochem. Biophys. Res. Commun. 328, 595−600
15 Arai, K., Lee, S. R., and Lo, E. H. (2003) Essential role for ERK mitogen-activated protein kinase in matrix metalloproteinase- 9 regulation in rat cortical astrocytes. Glia 43, 254−264
16 Min, K., Jou, I., and Joe, E. (2003) Plasminogen-induced IL-$1\beta$ and TNF-$\alpha$ production in microglia is regulated by reactive oxygen species. Biochem. Biophys. Res. Commun. 312, 969− 974
17 Starr, R. and Hilton, D. J. (1999) Negative regulation of the JAK/STAT pathway. Bioessays 21, 47−52
18 Endo, T. A., Masuhara, M., Yokouchi, M., Suzuki, R., Sakamoto, H., et al. (1997) A new protein containing an SH2 domain that inhibits JAK kinases. Nature 387, 921−924   DOI   ScienceOn
19 Choi, W. H., Ji, K. A., Jeon, S. B., Yang, M. S., Kim, H., et al. (2005) Anti-inflanmmatory roles of retinoic acid in rat brain astrocytes: Suppression of interferon-gamma-induced JAK/ STAT phosphorylation. Biochem. Biophys. Res. Commun. 329, 125−131
20 Cohen, S., Dovrat, S., Sarid, R., Huberman, E., and Salzberg, S. (2005) JAK-STAT signaling involved in phorbol 12- myristate 13-acetate-and dimethyl sulfoxide-induced 2′-5′ oligoadenylate synthetase expression in human HL-60 Leukemia cells. Leuk. Res. 29, 923−931
21 Hwang, J. I., Shin, K. J., Oh, Y. S., Choi, J. W., Lee, Z. W., et al. (2005) Phospholipase C-$\beta3$ mediates the thrombin-induced $Ca^{2+}$ response in glial cells. Mol. Cells 19, 375−381
22 Auernhammer, C. J., Bousquet, C., and Melmed, S. (1999) Autoregulation of pituitary corticotroph SOCS-3 expression: characterization of the murine SOCS-3 promoter. Proc. Natl. Acad. Sci. USA 96, 6964−6969
23 Chen, X. P., Losman, J. A., Cowan, S., Donahue, E., Fay, S., et al. (2002) Pim serine/threonine kinases regulate the stability of Socs-1 protein. Proc. Natl. Acad. Sci. USA 99, 2175−2180
24 Ehlting, C., Haussinger, D., and Bode, J. G. (2005) Sp3 is involved in the regulation of SOCS3 gene expression. Biochem. J. 387, 737−745
25 Ridet, J. L., Malhotra, S. K., Privat, A., and Gage, F. H. (1997) Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci. 20, 570−577   DOI
26 Amos, S., Martin, P. M., Polar, G. A., Parsons, S. J., and Hussaini, I. M. (2005) Phorbol 12-myristate 13-acetate induces epidermal growth factor receptor transactivation via protein kinase Cdelta/c-Src pathways in glioblastoma cells. J. Biol. Chem. 280, 7729−7738