Role of human LZIP in differential activation of the NF-κB pathway that is induced by CCR1-dependent chemokines

Human leucine zipper protein (LZIP) associates with CC chemokine receptor I (CCR I) and this protein-protein interaction should play an important role in leukocyte cell mobility. LZIP is known to regulate leukotactin-I (Lkn-I)-dependent cell migration without affecting the chemotactic activities of other CC chemokines that bind to CCR 1. Since Lkn-I is engaged in the transcriptional activation of nuclear factor kappa B (NF-kappa B) and subsequent activation of the chemoattractant ability of leukocytes, we investigated the regulatory role of LZIP in the NF-kappa B pathway that is induced by CCRI-dependent chemokines. LZIP increased NF-kappa B-dependent luciferase activity in response to Lkn-I in HOS/CCRI cells and THP-I cells. However, the NF-kappa B-dependent luciferase activities induced by other CCRI-dependent chemokines were not affected by LZIP overexpression. LZIP also increased Lkn-I-induced chemotactic activity through activation of the NF-kappa B pathway, whereas LZIP did not affect either the transactivation of NF-kappa B or the chemotactic activities induced by other CCRI-dependent chemokines. Western blot analysis showed that LZIP increased the degradation of I kappa B alpha induced by Lkn-I but not by other CCRI-dependent chemokines. Results from electrophoretic mobility shift assay (EMSA) showed that LZIP enhanced the Lkn-I-induced DNA-binding activity of NF-kappa B. These data indicate that LZIP functions as a positive regulator in the NF-kappa B activation pathway that is triggered by Lkn-I without affecting the transcriptional activation of NF-kappa B induced by other CCRI-dependent chemokines.