CXCL12 signaling is independent of Jak2 and Jak3

Masato Moriguchi, Bruce D. Hissong, Massimo Gadina, Kunihiro Yamaoka, H. Lee Tiffany, Philip M. Murphy, Fabio Candotti, John J. O'Shea

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Janus kinases (Jaks) are a small family of cytoplasmic tyrosine kinases, critical for signaling by Type I and II cytokine receptors. The importance of Jaks in signaling by these receptors has been firmly established by analysis of mutant cell lines, the generation of Jak knock-out mice, and the identification of patients with Jak3 mutations. While a number of other ligands that do not bind Type I and II cytokine receptors have also been reported to activate Jaks, the requirement for Jaks in signaling by these receptors is less clear. Chemokines for example, which bind seven transmembrane receptors, have been reported to activate Jaks, and principally through the use of pharmacological inhibitors, it has been argued that Jaks are essential for chemokine signaling. In the present study, we focused on CXCR4, which binds the chemokine CXCL12 or stromal cell-derived factor-1, a chemokine that has been reported to activate Jak2 and Jak3. We found that the lack of Jak3 had no effect on CXCL12 signaling or chemotaxis nor did overexpression of wild-type versions of the kinase. Similarly, overexpression of wild-type or catalytically inactive Jak2 or "knocking-down" Jak2 expression using siRNA also had no effect. We also found that in primary lymphocytes, CXCL12 did not induce appreciable phosphorylation of any of the Jaks compared with cytokines for which these kinases are required. Additionally, little or no Stat (signal transducer and activator of transcription) phosphorylation was detected. Thus, we conclude that in contrast to previous reports, Jaks, especially Jak3, are unlikely to play an essential role in chemokine signaling.

Original languageEnglish
Pages (from-to)17408-17414
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number17
DOIs
Publication statusPublished - 2005 Apr 29
Externally publishedYes

Fingerprint

Janus Kinases
Chemokines
Chemokine CXCL12
Phosphorylation
Cytokine Receptors
Phosphotransferases
Lymphocytes
Chemotaxis
Transcription
Transducers
Knockout Mice
Protein-Tyrosine Kinases
Small Interfering RNA
Cells
Pharmacology
Cytokines
Ligands
Cell Line
Mutation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Moriguchi, M., Hissong, B. D., Gadina, M., Yamaoka, K., Tiffany, H. L., Murphy, P. M., ... O'Shea, J. J. (2005). CXCL12 signaling is independent of Jak2 and Jak3. Journal of Biological Chemistry, 280(17), 17408-17414. https://doi.org/10.1074/jbc.M414219200

CXCL12 signaling is independent of Jak2 and Jak3. / Moriguchi, Masato; Hissong, Bruce D.; Gadina, Massimo; Yamaoka, Kunihiro; Tiffany, H. Lee; Murphy, Philip M.; Candotti, Fabio; O'Shea, John J.

In: Journal of Biological Chemistry, Vol. 280, No. 17, 29.04.2005, p. 17408-17414.

Research output: Contribution to journalArticle

Moriguchi, M, Hissong, BD, Gadina, M, Yamaoka, K, Tiffany, HL, Murphy, PM, Candotti, F & O'Shea, JJ 2005, 'CXCL12 signaling is independent of Jak2 and Jak3', Journal of Biological Chemistry, vol. 280, no. 17, pp. 17408-17414. https://doi.org/10.1074/jbc.M414219200
Moriguchi M, Hissong BD, Gadina M, Yamaoka K, Tiffany HL, Murphy PM et al. CXCL12 signaling is independent of Jak2 and Jak3. Journal of Biological Chemistry. 2005 Apr 29;280(17):17408-17414. https://doi.org/10.1074/jbc.M414219200
Moriguchi, Masato ; Hissong, Bruce D. ; Gadina, Massimo ; Yamaoka, Kunihiro ; Tiffany, H. Lee ; Murphy, Philip M. ; Candotti, Fabio ; O'Shea, John J. / CXCL12 signaling is independent of Jak2 and Jak3. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 17. pp. 17408-17414.
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