Src family kinases are necessary for cell migration induced by extracellular HMGB1.
HMGB1 is a nuclear protein that signals tissue damage, as it is released by cells dying traumatically or secreted by activated innate immunity cells. Extracellular HMGB1 elicits the migration to the site of tissue damage of several cell types, including inflammatory cells and stem cells. The identity of the signaling pathways activated by extracellular HMGB1 is not known completely: We reported previously that ERK and NF-kappaB pathways are involved, and we report here that Src is also activated. The ablation of Src or inhibition with the kinase inhibitor PP2 blocks migration toward HMGB1. Src associates to and mediates the phosphorylation of FAK and the formation of focal adhesions.
Palumbo
Roberta
R
San Raffaele Research Institute, 20132 Milano, Italy. palumbo.roberta@hsr.it
De Marchis
Francesco
F
Pusterla
Tobias
T
Conti
Antonio
A
Alessio
Massimo
M
Bianchi
Marco E
ME
D016475:3T3 Cells; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D020099:Coated Materials, Biocompatible / Q000378:metabolism; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007526:Isoelectric Point; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
C412373:AG 1879; D020099:Coated Materials, Biocompatible; D016895:Culture Media, Serum-Free; D005353:Fibronectins; D024243:HMGB1 Protein; D051419:Paxillin; D011743:Pyrimidines; D019061:src-Family Kinases