The Journal of Immunology, Vol 153, Issue 10 4436-4447, Copyright © 1994 by American Association of Immunologists

ARTICLES

Involvement of Janus kinases, p52shc, Raf-1, and MEK-1 in the IL-6- induced mitogen-activated protein kinase cascade of a growth-responsive B cell line

G Kumar, S Gupta, S Wang and AE Nel
Department of Medicine, UCLA School of Medicine 90024.

We have previously shown that the IL-6R in a growth-responsive B cell line, AF10, induces activation of mitogen-activated protein (MAP) kinase. Here we demonstrate the activation of Raf-1 and MEK-1, which act as a MAP kinase kinase kinase and a MAP kinase kinase, respectively, in the MAP kinase cascade induced by IL-6 in AF10 cells. IL-6 also induced tyrosine phosphorylation of the signaling transducing subunit of the IL-6R in AF10 cells, along with tyrosine phosphorylation of the gp130-associated tyrosine protein kinase JAK1 and the adaptor molecule p52shc. Although induction of tyrosine phosphorylation and activation of MAP kinase by IL-6 in a differentiation-responsive B cell line, SKW 6.4, were below the limits of detection, the phorbol ester PMA did activate Raf-1, MEK-1, and MAP kinase without inducing the phosphorylation of gp130, JAKs, or p52shc. These results suggest that JAK kinase family members associated with the IL-6R may participate in the activation of MAP kinase in AF10 cells by way of an adaptor protein and Ras-dependent kinase cascade.

This article has been cited by other articles:

				S. M. Akula, P. W. Ford, A. G. Whitman, K. E. Hamden, B. A. Bryan, P. P. Cook, and J. A. McCubrey B-Raf-dependent expression of vascular endothelial growth factor-A in Kaposi sarcoma-associated herpesvirus-infected human B cells Blood, June 1, 2005; 105(11): 4516 - 4522. [Abstract] [Full Text] [PDF]

				J. Laflamme, A. Akoum, and P. Leclerc Induction of human sperm capacitation and protein tyrosine phosphorylation by endometrial cells and interleukin-6 Mol. Hum. Reprod., February 1, 2005; 11(2): 141 - 150. [Abstract] [Full Text] [PDF]

				S. Zvonic, J. C. Hogan, P. Arbour-Reily, R. L. Mynatt, and J. M. Stephens Effects of Cardiotrophin on Adipocytes J. Biol. Chem., November 12, 2004; 279(46): 47572 - 47579. [Abstract] [Full Text] [PDF]

				J. D. French, D. K. Walters, and D. F. Jelinek Transactivation of gp130 in Myeloma Cells J. Immunol., April 1, 2003; 170(7): 3717 - 3723. [Abstract] [Full Text] [PDF]

				M. A. Frassanito, A. Cusmai, G. Iodice, and F. Dammacco Autocrine interleukin-6 production and highly malignant multiple myeloma: relation with resistance to drug-induced apoptosis Blood, January 15, 2001; 97(2): 483 - 489. [Abstract] [Full Text] [PDF]

				S. A. JONES, S. HORIUCHI, N. TOPLEY, N. YAMAMOTO, and G. M. FULLER The soluble interleukin 6 receptor: mechanisms of production and implications in disease FASEB J, January 1, 2001; 15(1): 43 - 58. [Abstract] [Full Text] [PDF]

				A. Badache and N. E. Hynes Interleukin 6 Inhibits Proliferation and, in Cooperation with an Epidermal Growth Factor Receptor Autocrine Loop, Increases Migration of T47D Breast Cancer Cells Cancer Res., January 1, 2001; 61(1): 383 - 391. [Abstract] [Full Text]

				T. Hideshima, D. Chauhan, G. Teoh, N. Raje, S. P. Treon, Y.-T. Tai, Y. Shima, and K. C. Anderson Characterization of Signaling Cascades Triggered by Human Interleukin-6 versus Kaposi's Sarcoma-associated Herpes Virus-encoded Viral Interleukin 6 Clin. Cancer Res., March 1, 2000; 6(3): 1180 - 1189. [Abstract] [Full Text]

				S. Rivest, S. Lacroix, L. Vallières, S. Nadeau, J. Zhang, and N. Laflamme How the Blood Talks to the Brain Parenchyma and the Paraventricular Nucleus of the Hypothalamus During Systemic Inflammatory and Infectious Stimuli Experimental Biology and Medicine, January 1, 2000; 223(1): 22 - 38. [Abstract] [Full Text]

				G. Muller-Newen, A. Kuster, U. Hemmann, R. Keul, U. Horsten, A. Martens, L. Graeve, J. Wijdenes, and P. C. Heinrich Soluble IL-6 Receptor Potentiates the Antagonistic Activity of Soluble gp130 on IL-6 Responses J. Immunol., December 1, 1998; 161(11): 6347 - 6355. [Abstract] [Full Text] [PDF]

				F.-h. Xu, S. Sharma, A. Gardner, Y. Tu, A. Raitano, C. Sawyers, and A. Lichtenstein Interleukin-6-Induced Inhibition of Multiple Myeloma Cell Apoptosis: Support for the Hypothesis That Protection Is Mediated Via Inhibition of the JNK/SAPK Pathway Blood, July 1, 1998; 92(1): 241 - 251. [Abstract] [Full Text] [PDF]

				F. M. Botelho, D. R. Edwards, and C. D. Richards Oncostatin M Stimulates c-Fos to Bind a Transcriptionally Responsive AP-1 Element within the Tissue Inhibitor of Metalloproteinase-1 Promoter J. Biol. Chem., February 27, 1998; 273(9): 5211 - 5218. [Abstract] [Full Text] [PDF]

				M. Hallek, P. Leif Bergsagel, and K. C. Anderson Multiple Myeloma: Increasing Evidence for a Multistep Transformation Process Blood, January 1, 1998; 91(1): 3 - 21. [Full Text] [PDF]

				D. Chauhan, S. Kharbanda, A. Ogata, M. Urashima, G. Teoh, M. Robertson, D. W. Kufe, and K. C. Anderson Interleukin-6 Inhibits Fas-Induced Apoptosis and Stress-Activated Protein Kinase Activation in Multiple Myeloma Cells Blood, January 1, 1997; 89(1): 227 - 234. [Abstract] [Full Text] [PDF]

				L. C. Berger and R. G. Hawley Interferon-beta Interrupts Interleukin-6-Dependent Signaling Events in Myeloma Cells Blood, January 1, 1997; 89(1): 261 - 271. [Abstract] [Full Text] [PDF]

				M. Ernst, A. Oates, and A. R. Dunn gp130-mediated Signal Transduction in Embryonic Stem Cells Involves Activation of Jak and Ras/Mitogen-activated Protein Kinase Pathways J. Biol. Chem., November 22, 1996; 271(47): 30136 - 30143. [Abstract] [Full Text] [PDF]

				D. T. Kulas, G. G. Freund, and R. A. Mooney The Transmembrane Protein-tyrosine Phosphatase CD45 Is Associated with Decreased Insulin Receptor Signaling J. Biol. Chem., January 12, 1996; 271(2): 755 - 760. [Abstract] [Full Text] [PDF]

				C.-F. Lai, J. Ripperger, K. K. Morella, Y. Wang, D. P. Gearing, G. H. Fey, and H. Baumann Separate Signaling Mechanisms Are Involved in the Control of STAT Protein Activation and Gene Regulation via the Interleukin 6 Response Element by the Box 3 Motif of gp130 J. Biol. Chem., June 23, 1995; 270(25): 14847 - 14850. [Abstract] [Full Text] [PDF]

				Y. Wang, O. Robledo, E. Kinzie, F. Blanchard, C. Richards, A. Miyajima, and H. Baumann Receptor Subunit-specific Action of Oncostatin M in Hepatic Cells and Its Modulation by Leukemia Inhibitory Factor J. Biol. Chem., August 11, 2000; 275(33): 25273 - 25285. [Abstract] [Full Text] [PDF]

				H. M. Hermanns, S. Radtke, F. Schaper, P. C. Heinrich, and I. Behrmann Non-redundant Signal Transduction of Interleukin-6-type Cytokines. THE ADAPTER PROTEIN Shc IS SPECIFICALLY RECRUITED TO THE ONCOSTATIN M RECEPTOR J. Biol. Chem., December 22, 2000; 275(52): 40742 - 40748. [Abstract] [Full Text] [PDF]