The CXCR1 tail mediates beta1 integrin-dependent cell migration via MAP kinase signaling.
In this study, we examined how IL-8 induces leukocyte migration on major beta1 integrin ligands derived from the extracellular matrix protein fibronectin. We assessed individual contributions of signaling by IL-8 receptors by transfection of CXCR1 and CXCR2 into rat basophilic leukemia (RBL) cells and human monocytic THP-1 cells. CXCR1 expressing cells migrated on the fibronectin ligands for alpha4beta1 and alpha5beta1 integrins in response to IL-8, whereas CXCR2 expressing cells did not. RBL cells expressing the chimeric CXCR1 receptor containing the cytoplasmic tail of CXCR2 had greatly blunted migration, while cells expressing the CXCR2 chimera with the tail of CXCR1 had augmented migration. Last, inhibitors of p38 and JNK MAP kinases blocked IL-8-induced migration in CXCR1+ cells. We conclude that IL-8 stimulated beta1 integrin-mediated leukocyte migration on fibronectin through CXCR1 is dependent on the C-terminal cytoplasmic domain of CXCR1 and subsequent p38 and JNK MAPK signaling.
Liu-Bryan
Ru
R
Department of Medicine, Veterans Affairs Medical Center, University of California, San Diego, CA, USA.
Pay
Salih
S
Schraufstatter
Ingrid U
IU
Rose
David M
DM
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D007962:Leukocytes / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051381:Rats; D023062:Receptors, Interleukin-8A / Q000737:chemistry / Q000378:metabolism*; D023063:Receptors, Interleukin-8B / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
D019012:Integrin beta1; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D020928:Mitogen-Activated Protein Kinases