Advertisement

Research Article Free access | 10.1172/JCI119344

Cytokine signaling through the novel tyrosine kinase RAFTK in Kaposi's sarcoma cells.

Z Y Liu, R K Ganju, J F Wang, M A Ona, W C Hatch, T Zheng, S Avraham, P Gill, and J E Groopman

Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

Find articles by Liu, Z. in: JCI | PubMed | Google Scholar

Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

Find articles by Ganju, R. in: JCI | PubMed | Google Scholar

Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

Find articles by Wang, J. in: JCI | PubMed | Google Scholar

Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

Find articles by Ona, M. in: JCI | PubMed | Google Scholar

Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

Find articles by Hatch, W. in: JCI | PubMed | Google Scholar

Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

Find articles by Zheng, T. in: JCI | PubMed | Google Scholar

Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

Find articles by Avraham, S. in: JCI | PubMed | Google Scholar

Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

Find articles by Gill, P. in: JCI | PubMed | Google Scholar

Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

Find articles by Groopman, J. in: JCI | PubMed | Google Scholar

Published April 1, 1997 - More info

Published in Volume 99, Issue 7 on April 1, 1997
J Clin Invest. 1997;99(7):1798–1804. https://doi.org/10.1172/JCI119344.
© 1997 The American Society for Clinical Investigation
Published April 1, 1997 - Version history
View PDF
Abstract

A number of cytokines, including basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), oncostatin M (OSM), IL-6, and tumor necrosis factor alpha (TNF-alpha), have been postulated to have a role in the pathogenesis of Kaposi's sarcoma (KS). The proliferative effects of bFGF and OSM may be via their reported activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway in KS cells. We now report that KS cells express a recently identified focal adhesion kinase termed RAFTK which appears in other cell systems to coordinate surface signals between cytokine and integrin receptors and the cytoskeleton as well as act downstream to modulate JNK activation. We also report that the tyrosine kinase receptor FLT-4, present on normal lymphatic endothelium, is robustly expressed in KS cells. Treatment of KS cells with VEGF-related protein (VRP), the ligand for the FLT-4 receptor, as well as with the cytokines bFGF, OSM, IL-6, VEGF, or TNF-alpha resulted in phosphorylation and activation of RAFTK. Following its activation, there was an enhanced association of RAFTK with the cytoskeletal protein paxillin. This association was mediated by the hydrophobic COOH-terminal domain of the kinase. Furthermore, JNK activity was increased in KS cells after VEGF or VRP stimulation. We postulate that in these tumor cells RAFTK may be activated by a diverse group of stimulatory cytokines and facilitate signal transduction to the cytoskeleton and downstream to the growth promoting JNK pathway.

Version history
  • Version 1 (April 1, 1997): No description
Advertisement
Advertisement