Human LZIP binds to CCR1 and differentially affects the chemotactic activities of CCR1‐dependent chemokines

Abstract

Signaling molecules that bind to chemokine receptors should play key roles in regulation of cell migration induced by chemokines. To characterize the CCR1-mediated cellular signal transduction mechanism, we used the yeast two-hybrid system to identify a cellular ligand for CCR1. LZIP, which has been known as a transcription factor in various cell types, was identified as a CCR1 binding protein. Although the ability of LZIP to bind DNA is possibly what allows it to function as a transcription factor, its detailed function and participation in chemotaxis have not been established. We found that LZIP binds to CCR1 based on results of a mammalian two-hybrid assay and immunoprecipitation experiments. The 21-260 residues of LZIP were essential for interaction with CCR1. Results from a chemotaxis assay using LZIP transfected cells showed that LZIP enhanced Lkn-1-induced chemotaxis, whereas the chemotactic activities induced by other CC chemokines that bind to CCR1, including MIP-1alpha, RANTES, or HCC-4, were not affected by LZIP overexpression. These data indicate that LZIP binds to CCR1 and that the interaction between CCR1 and LZIP participates in regulation of Lkn-1-dependent cell migration without affecting the chemotactic activities of other CC chemokines that bind to CCR1.

Human LZIP induces monocyte CC chemokine receptor 2 expression leading to enhancement of monocyte chemoattractant protein 1/CCL2-induced cell migration

“…LZIP also increased CCR1 mRNA expression. Our previous report suggests that LZIP functions as a cellular modulator of CCR1-dependent chemokines and is involved in Lkn-1-induced cell migration (Ko et al, 2004). CCR1 mRNA expression in THP-1 cells transfected with the mock vector was very low, however, cells transfected with LZIP showed an increase in CCR1 mRNA expression.…”

“…However, the chemotactic activity of MIP-1α, used as a negative control in LZIP transfected cells, was comparable with cells transfected with the mock vector ( Figure 4B). We generated siRNA for LZIP (siLZIP) that can reduce the expression of LZIP to 0-50% of the endogenous level (Ko et al, 2004). Transfection experiments with LZIP and siLZIP reduced the chemotactic activities of MCP-1 and Lkn-1 in cells transfected with LZIP alone by 37% and 40%, respectively ( Figure 4B).…”

“…However, the exact biological role and the natural target genes of LZIP have not been characterized. Although there is controversy regarding the localization of endogenous LZIP, we have reported that LZIP physically interacts with CCR1 and participates in regulation of leukotactin (Lkn)-1/CCL15-induced cell migration without affecting the chemotactic activities of other CCR1-binding chemokines (Ko et al, 2004). We have also proposed that LZIP acts as a positive regulator in the NF-κB activation pathway that is triggered by Lkn-1, causing enhancement of Lkn-1-induced migration of monocytes (Jang et al, 2007a).…”

Identification and molecular characterization of cellular factors required for glucocorticoid receptor-mediated mRNA decay

“…The chemotaxis assay was performed as described previously (Ko et al 2004;Jang et al 2007;Cho et al 2015). In brief, chemotaxis assay was carried out using a 48-well chemotaxis microchamber (Neuroprobe).…”

Human Leucine Zipper Protein sLZIP Induces Migration and Invasion of Cervical Cancer Cells via Expression of Matrix Metalloproteinase-9

“…Ubiquitously expressed human LZIP binds to the canonical cAMP-responsive element (CRE) and regulates cell proliferation (22,23). It has been reported that human LZIP binds to CC chemokine receptor 1 and is a positive regulator in CC chemokine leukotactin-1-induced cell migration (24). We previously identified a novel isoform of human LZIP and par-tially characterized the differential roles of two human LZIP isoforms (25).…”