Identification of a Novel Type I Cytokine Receptor CRL2 Preferentially Expressed by Human Dendritic Cells and Activated Monocytes
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文摘
From human dendritic cell (DC) cDNA library, we identified a novel type I cytokine receptor, designated as cytokine receptor-like molecule 2 (CRL2). CRL2 cDNA encoded a 371-residue type I transmembrane protein with an extracellular domain of 210 residues and an intracellular domain of 119 residues. Its extracellular domain contains conserved cysteine residues and WAS-like motif in place of the hallmark of WSXWS motif present in other type I cytokine receptors. The intracellular domain contained a membrane-proximal “box 1” motif and conserved tyrosine residue potentially as a binding site for signal transducing molecules. CRL2 protein shares significant homology with common cytokine receptor (γc) and interleukin-13 receptor α1 chain. Northern blot analysis showed that CRL2 was restrictedly expressed by spleen and peripheral blood leukocytes, and abundantly expressed by HL-60 cells. RT-PCR analysis demonstrated that CRL2 was preferentially expressed by DC and monocytes. Interestingly, CRL2 expression was up-regulated when monocytes were activated by LPS. These indicate that CRL2 may be involved in the biological functions of DC and monocytes. The Ba/F3 transfectants of CRL2 was retrovirally established with the expressed FLAG-tagged CRL2 in the size of approximately 48 kD, which could be efficiently immunoprecipitated. We also prepared CRL2Ig fusion protein. The identification of its ligand and involvement of signal transduction will help to elucidate its potential function.