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The JAK‐STAT pathway regulation of endothelial cell migration and differentiation
Author(s) -
Kovala A. Thomas,
Clark Thomas,
Rossi Laura
Publication year - 2013
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/fasebj.27.1_supplement.604.2
Subject(s) - jak stat signaling pathway , microbiology and biotechnology , angiogenesis , stat protein , janus kinase , transactivation , matrigel , stat , stat3 , signal transduction , vascular endothelial growth factor , chemistry , vascular endothelial growth factor a , biology , cancer research , transcription factor , receptor tyrosine kinase , biochemistry , gene , vegf receptors
Cell migration and differentiation are both fundamental processes in angiogenesis. We investigated the role of the Janus kinase (JAK)‐signal transducer and activator of transcription (STAT) pathway in endothelial migration and differentiation. Matrigel tube formation assays were used to examine endothelial differentiation following stimulation with vascular endothelial growth factor (VEGF) or sphingosine 1‐phosphate (S1P), a lipid activator of angiogenesis. VEGF receptor 2 inhibitors blocked tube formation induction by both S1P and VEGF, supporting a transactivation mechanism. These inhibitors also blocked JAK activation, demonstrating the involvement of S1P‐induced transactivation of the VEGF receptor 2. A JAK inhibitor blocked differentiation induced by either ligand, implicating the JAK‐STAT pathway in regulation of the process. STAT5 inhibition significantly inhibited differentiation. Signalling pathways involve the ERK cascade, Src and NF‐κB were also found to play important roles differentiation. The migration of endothelial cells was studied using a modified Boyden chamber assay and the inhibition of the JAK‐STAT pathway blocked migration. The STAT3 and STAT5 pathways were both found to play important roles in migration. Angiogenic processes induced by both VEGF and S1P require activation of multiple signalling pathways, including JAK‐STAT pathways.