Signalling through Src family kinase isoforms is not redundant in models of thrombo-inflammatory vascular disease.

Signalling through Src family kinase isoforms is not redundant in models of thrombo-inflammatory vascular disease.
J Cell Mol Med. 2018 Jul 04;:
Authors: Harrison MJ, Chimen M, Hussain M, Iqbal AJ, Senis YA, Nash GB, Watson SP, Rainger GE
Abstract
The Src family kinases (SFK) are a group of signalling molecules with important regulatory functions in inflammation and haemostasis. Leucocytes and platelets express multiple isoforms of the SFKs. Previous studies used broad-spectrum pharmacological inhibitors, or murine models deficient in multiple SFK isoforms, to demonstrate the functional consequences of deficiencies in SFK signalling. Here, we hypothesized that individual SFK operate in a non-redundant fashion in the thrombo-inflammatory recruitment of monocyte during atherosclerosis. Using in vitro adhesion assays and single SFK knockout mice crossed with the ApoE-/- model of atherosclerosis, we find that SFK signalling regulates platelet-dependent recruitment of monocytes. However, loss of a single SFK, Fgr or Lyn, reduced platelet-mediated monocyte recruitment in vitro. This translated into a significant reduction in the burden of atherosclerotic disease in Fgr-/- /ApoE-/- or Lyn-/- /ApoE-/- animals. SFK signalling is not redundant in thrombo-inflammatory vascular disease and individual SFK may represent targets for therapeutic intervention.
PMID: 29974666 [PubMed - as supplied by publisher]

Source: J Cell Mol Med - July 4, 2018 Category: Molecular Biology Authors: Harrison MJ, Chimen M, Hussain M, Iqbal AJ, Senis YA, Nash GB, Watson SP, Rainger GE Tags: J Cell Mol Med Source Type: research