Human LZIP binds to CCR1 and differentially affects the chemotactic activities of CCR1-dependent chemokines.
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.
Ko
Jesang
J
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea. jesangko@amc.seoul.kr
Jang
Sung-Wuk
SW
Kim
Yoon Suk
YS
Kim
In Sik
IS
Sung
Ho Joong
HJ
Kim
Hong-Hee
HH
Park
Joong-Yeol
JY
Lee
Young Han
YH
Kim
Jiyoung
J
Na
Doe Sun
DS
D000818:Animals; D001483:Base Sequence; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D019742:Chemokines, CC / Q000494:pharmacology* / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects* / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D017362:Cyclic AMP Response Element-Binding Protein; D006801:Humans; D007668:Kidney; D016350:Leucine Zippers / Q000235:genetics / Q000502:physiology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000494:pharmacology; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D017384:Sequence Deletion; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques
C481939:CCL16 protein, human; C515300:CCR1 protein, human; C107941:CREB3 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D017362:Cyclic AMP Response Element-Binding Protein; D019402:Macrophage Inflammatory Proteins; D034741:RNA, Small Interfering; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors