TY - JOUR AU - Wang, Liqing AU - Xiong, Qiuhong AU - Li, Ping AU - Chen, Guangxin AU - Tariq, Nayab AU - Wu, Changxin PY - 2021 DA - 2021/01/23 TI - The negative charge of the 343 site is essential for maintaining physiological functions of CXCR4 JO - BMC Molecular and Cell Biology SP - 8 VL - 22 IS - 1 AB - Warts, hypogammaglobulinemia, recurrent bacterial infections and myelokathexis (WHIM) syndrome is a primary immunodeficiency disease (PID) usually caused by autosomal dominant mutations in the chemokine receptor CXCR4 gene. To date, a total of nine different mutations including eight truncation mutations and one missense mutation (E343K, CXCR4E343K) distributed in the C-terminus of CXCR4 have been identified in humans. Studies have clarified that the loss of phosphorylation sites in the C-terminus of truncated CXCR4 impairs the desensitization process, enhances the activation of G-protein, prolongs downstream signaling pathways and introduces over immune responses, thereby causing WHIM syndrome. So far, there is only one reported case of WHIM syndrome with a missense mutation, CXCR4E343K, which has a full length of C-terminus with entire phosphorylation sites, no change in all potential phosphorylation sites. The mechanism of the missense mutation (CXCR4E343K) causing WHIM syndrome is unknown. This study aimed to characterize the effect of mutation at the 343 site of CXCR4 causing the replacement of arginine/E with glutamic acid/K on the receptor signal transduction, and elucidate the mechanism underling CXCR4E343K causing WHIM in the reported family. SN - 2661-8850 UR - https://doi.org/10.1186/s12860-021-00347-9 DO - 10.1186/s12860-021-00347-9 ID - Wang2021 ER -