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IL‐1 induced release of Ca 2+ from internal stores is dependent on cell‐matrix interactions and regulates ERK activation
Author(s) -
Wang Qin,
Downey Gregory P.,
Choi Christine,
Kapus András,
Mcculloch Christopher A.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0069fje
Subject(s) - focal adhesion , microbiology and biotechnology , fibronectin , thapsigargin , extracellular matrix , adhesion , mapk/erk pathway , chemistry , endoplasmic reticulum , cell adhesion , integrin , extracellular , signal transduction , cell , biology , biochemistry , organic chemistry
The cellular mechanisms that modulate interleukin‐1 (IL‐1) signaling are not defined. In fibroblasts, IL‐1 signaling is affected by the nature of cell‐matrix adhesions including focal adhesions, adhesive domains that sequester IL‐1 receptors. We conducted studies to elucidate which steps of cellular Ca 2+ handling are affected by focal adhesions and by which mechanisms focal adhesions modulate IL‐1‐induced Ca 2+ signals and ERK activation in human gingival fibroblasts. Cells were plated on poly‐ L ‐lysine or fibronectin and treated with tenascin, Hep‐I, or SPARC peptides to inhibit focal adhesion formation. These treatments blocked IL‐1 and thapsigargin‐induced Ca 2+ release from the endoplasmic reticulum, indicating that the ER‐release pathway is focal adhesion dependent. Focal adhesions were also required for Ca 2+ entry through store‐operated channels and for IL‐1‐induced ERK activation. Thus interactions with the extracellular matrix and focal adhesion formation regulate IL‐1‐induced generation of intracellular Ca 2+ signals that in turn are required for ERK activation.