This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, Y.-M. Articles by Kung, H.-J. Search for Related Content PubMed PubMed Citation Articles by Wu, Y.-M. Articles by Kung, H.-J.

Signal Pathways in Up-regulation of Chemokines by Tyrosine Kinase MER/NYK in Prostate Cancer Cells

University of California at Davis, University of California Davis Cancer Center, Sacramento, California

The AXL/UFO family of tyrosine kinases is characterized by a common N-CAM (neural adhesion molecule)–related extracellular domain and a common ligand, GAS6 (growth arrest-specific protein 6). Family members are prone to transcriptional regulation and carry out diverse functions including the regulation of cell adhesion, migration, phagocytosis, and survival. In this report, we describe a new role of MER/N-CAM–related kinase (NYK), a member of the AXL family of kinases, in the up-regulation of chemokines in prostate cancer cells. We show that NYK has elevated expression in a subset of tumor specimens and prostate cancer cell lines. Activation of NYK in the prostate cancer cell line DU145 does not cause a mitogenic effect; instead, it causes a differentiation phenotype. Microarray analysis revealed that NYK is a strong inducer of endocrine factors including interleukin (IL)-8 and several other angiogenic CXC chemokines as well as bone morphogenic factors. The dramatic increase of IL-8 expression is seen at both transcriptional and posttranscriptional levels. The downstream signals engaged by NYK were characterized, and those responsible for the up-regulation of IL-8 transcription were defined. In contrast to IL-1, NYK-induced up-regulation of IL-8 in DU145 depends on the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase/Jun/Fos pathway, but not phosphoinositide 3'-kinase/nuclear factor-B. These data define a new function of the AXL family of kinases and suggest a potential role of NYK in prostate cancer progression.

This article has been cited by other articles:

				J.-D. Lay, C.-C. Hong, J.-S. Huang, Y.-Y. Yang, C.-Y. Pao, C.-H. Liu, Y.-P. Lai, G.-M. Lai, A.-L. Cheng, I.-J. Su, et al. Sulfasalazine Suppresses Drug Resistance and Invasiveness of Lung Adenocarcinoma Cells Expressing AXL Cancer Res., April 15, 2007; 67(8): 3878 - 3887. [Abstract] [Full Text] [PDF]

				N. P. Mahajan, Y. E. Whang, J. L. Mohler, and H. S. Earp Activated Tyrosine Kinase Ack1 Promotes Prostate Tumorigenesis: Role of Ack1 in Polyubiquitination of Tumor Suppressor Wwox Cancer Res., November 15, 2005; 65(22): 10514 - 10523. [Abstract] [Full Text] [PDF]

				S. J. Holland, M. J. Powell, C. Franci, E. W. Chan, A. M. Friera, R. E. Atchison, J. McLaughlin, S. E. Swift, E. S. Pali, G. Yam, et al. Multiple Roles for the Receptor Tyrosine Kinase Axl in Tumor Formation Cancer Res., October 15, 2005; 65(20): 9294 - 9303. [Abstract] [Full Text] [PDF]