'Tuning' of type I interferon-induced Jak-STAT1 signaling by calcium-dependent kinases in macrophages. Academic Article uri icon

Overview

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-alpha-induced Jak activation and STAT1-dependent gene expression. CaMK inhibition suppressed STAT1-mediated interferon-alpha 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.

publication date

  • December 16, 2007

Research

keywords

  • Calcium-Calmodulin-Dependent Protein Kinase Kinase
  • Focal Adhesion Kinase 2
  • Interferon Type I
  • Janus Kinases
  • Macrophages
  • STAT1 Transcription Factor

Identity

Scopus Document Identifier

  • 38449093322

PubMed ID

  • 18084294

Additional Document Info

volume

  • 9

issue

  • 2