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Interaction of PRP4 with Krüppel-Like Factor 13 Regulates CCL5 Transcription¹

Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305

Activation of resting T lymphocytes initiates differentiation into mature effector cells over 3–7 days. The chemokine CCL5 (RANTES) and its major transcriptional regulator, Krüppel-like factor 13 (KLF13), are expressed late (3–5 days) after activation in T lymphocytes. Using yeast two-hybrid screening of a human thymus cDNA library, PRP4, a serine/threonine protein kinase, was identified as a KLF13-binding protein. Specific interaction of KLF13 and PRP4 was confirmed by reciprocal coimmunoprecipitation. PRP4 is expressed in PHA-stimulated human T lymphocytes from days 1 and 7 with a peak at day 3. Using an in vitro kinase assay, it was found that PRP4 phosphorylates KLF13. Furthermore, although phosphorylation of KLF13 by PRP4 results in lower binding affinity to the A/B site of the CCL5 promoter, coexpression of PRP4 and KLF13 increases nuclear localization of KLF13 and CCL5 transcription. Finally, knock-down of PRP4 by small interfering RNA markedly decreases CCL5 expression in T lymphocytes. Thus, PRP4-mediated phosphorylation of KLF13 plays a role in the regulation of CCL5 expression in T lymphocytes.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant (to A.M.K.) from the National Institutes of Health (NIH R37 DK35008-23). A.M.K. is the Shelagh Galligan Professor of Pediatrics.

² Address correspondence and reprint requests to Dr. Alan M. Krensky, Division of Immunology and Transplantation Biology, Stanford University, 300 Pasteur Drive, Stanford, CA 94305. E-mail address: krensky{at}stanford.edu

³ Abbreviations used in this paper: KLF13, Krüppel-like factor 13; HA, hemagglutinin; siRNA, small interfering RNA; RT-qPCR, real-time quantitative PCR; NLK, Nemo-like kinase; GUS, -glucuronidase; Brg-1, Brahma-related gene 1; Ct, threshold cycle; CBP, CREB binding protein; PCAF, p300/CBP-associated factor.