RAC1/P38 MAPK signaling pathway controls beta1 integrin-induced interleukin-8 production in human natural killer cells.
The MAP kinase (MAPK) p38 plays a key role in regulating inflammatory responses. Here, we demonstrate that beta1 integrin ligation on human NK cells results in the activation of the p38 MAPK signaling pathway, which is required for integrin-triggered IL-8 production. In addition, we identified some of the upstream events accompanying the beta1 integrin-mediated p38 MAPK activation, namely, the activation of the Rac guanine nucleotide exchange factor (GEF) p95 Vav, the small G protein Rac1, and the cytoplasmic kinases Pak1 and MKK3. Finally, we provide direct evidence that p95 Vav and Rac control the activation of p38 MAPK triggered by beta1 integrins.
Mainiero
F
F
Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome La Sapienza, Italy.
Soriani
A
A
Strippoli
R
R
Jacobelli
J
J
Gismondi
A
A
Piccoli
M
M
Frati
L
L
Santoni
A
A
D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D048371:MAP Kinase Kinase 3; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000378:metabolism*; D054462:p21-Activated Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D005353:Fibronectins; D019012:Integrin beta1; D016209:Interleukin-8; D017469:Receptors, Fibronectin; D011505:Protein-Tyrosine Kinases; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048371:MAP Kinase Kinase 3; C482530:MAP2K3 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D020830:rac1 GTP-Binding Protein