Abstract

Immunoreceptor tyrosine-based activation motif (ITAM)–coupled receptors modulate the amplitude and nature of macrophage responses to Toll-like receptor and cytokine receptor stimulation. However, the molecular mechanisms enabling this receptor crosstalk are not known. Here we investigated the function of the calcium-dependent kinases CaMK and Pyk2 'downstream' of ITAM-associated receptors in the regulation of cytokine-induced activation of Jak kinases and STAT transcription factors. CaMK and Pyk2 relayed signals from integrins and the ITAM-containing adaptor DAP12 to augment interleukin 10– and interferon--induced Jak activation and STAT1-dependent gene expression. CaMK inhibition suppressed STAT1-mediated interferon- signaling in a mouse model of systemic lupus erythematosus. Our results associate Pyk2 and Jak kinases with the linkage of signals emanating from cytokine and heterologous ITAM-dependent receptors.

1. Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, New York 10021, USA.
2. Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York 10021, USA.
3. Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
4. Departments of Orthopedics and of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
5. Graduate Program in Immunology and Microbial Pathogenesis, Weill Graduate School of Medical Sciences of Cornell University, New York, New York 10021, USA.
6. Present address: University of Crete Medical School, Heraklion Crete 71300, Greece.
7. These authors contributed equally to this work.

Correspondence to: Lionel B Ivashkiv^1,5 e-mail: ivashkivl@hss.edu

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

NPG Journals

by Subject Area

• Chemistry

  • Chemistry
  • Drug discovery
  • Biotechnology
  • Materials
  • Methods & Protocols

• Clinical Practice & Research

  • Cancer
  • Cardiovascular medicine
  • Dentistry
  • Endocrinology
  • Gastroenterology & Hepatology
  • Methods & Protocols
  • Pathology & Pathobiology
  • Urology

• Earth & Environment

  • Earth sciences
  • Evolution & Ecology

• Life sciences

  • Biotechnology
  • Cancer
  • Development
  • Drug discovery
  • Evolution & Ecology
  • Genetics
  • Immunology
  • Medical research
  • Methods & Protocols
  • Microbiology
  • Molecular cell biology
  • Neuroscience
  • Pharmacology
  • Systems biology

• Physical sciences

  • Physics
  • Materials

by A - Z Index