Role of human LZIP in differential activation of the NF-kappaB pathway that is induced by CCR1-dependent chemokines.
Human leucine zipper protein (LZIP) associates with CC chemokine receptor 1 (CCR1) and this protein-protein interaction should play an important role in leukocyte cell mobility. LZIP is known to regulate leukotactin-1 (Lkn-1)-dependent cell migration without affecting the chemotactic activities of other CC chemokines that bind to CCR1. Since Lkn-1 is engaged in the transcriptional activation of nuclear factor kappaB (NF-kappaB) and subsequent activation of the chemoattractant ability of leukocytes, we investigated the regulatory role of LZIP in the NF-kappaB pathway that is induced by CCR1-dependent chemokines. LZIP increased NF-kappaB-dependent luciferase activity in response to Lkn-1 in HOS/CCR1 cells and THP-1 cells. However, the NF-kappaB-dependent luciferase activities induced by other CCR1-dependent chemokines were not affected by LZIP overexpression. LZIP also increased Lkn-1-induced chemotactic activity through activation of the NF-kappaB pathway, whereas LZIP did not affect either the transactivation of NF-kappaB or the chemotactic activities induced by other CCR1-dependent chemokines. Western blot analysis showed that LZIP increased the degradation of IkappaBalpha induced by Lkn-1 but not by other CCR1-dependent chemokines. Results from electrophoretic mobility shift assay (EMSA) showed that LZIP enhanced the Lkn-1-induced DNA-binding activity of NF-kappaB. These data indicate that LZIP functions as a positive regulator in the NF-kappaB activation pathway that is triggered by Lkn-1 without affecting the transcriptional activation of NF-kappaB induced by other CCR1-dependent chemokines.
Jang
Sung-Wuk
SW
School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
Kim
Yoon Suk
YS
Lee
Young Han
YH
Ko
Jesang
J
D045744:Cell Line, Tumor; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism / Q000494:pharmacology; D019742:Chemokines, CC / Q000378:metabolism / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D015846:Monokines / Q000378:metabolism / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D012516:Osteosarcoma; D034741:RNA, Small Interfering; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
C515456:CCL11 protein, human; C108814:CCL15 protein, human; C515300:CCR1 protein, human; C107941:CREB3 protein, human; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D017362:Cyclic AMP Response Element-Binding Protein; D020672:I-kappa B Proteins; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D034741:RNA, Small Interfering; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D000072000:NF-KappaB Inhibitor alpha; D008156:Luciferases