Meuleners, Andrea Marie

Stimulation of T lymphocytes with stromal cell‐derived factor‐1alpha (SDF‐1alpha/CXCL12) results in colocalization of the chemokine receptor, CXCR4, and the T cell receptor (TCR). Internalization of the colocalized complex can initiate prolonged activation of the extracellular signal‐regulated kinases (ERK) ERK1 and ERK2, gene transcription, cytokine expression and migration. The molecular mechanisms behind the internalization of the colocalized complex are incompletely characterized. In this study, we show that there are multiple sites in the CXCR4 C‐terminus that influence the internalization of the CXCR4/TCR complex in Jurkat and JRT3 T cells. A mutation of amino acids 328 and 329 in the CXCR4 C‐terminus, an important beta‐arrestin binding site, significantly reduced internalization in Jurkat cells. Deletion mutations in the CXCR4 C‐terminus also significantly reduced internalization in Jurkat cells. Basal internalization in Jurkat cells was decreased by an element(s) in amino acids 342–352. Basal internalization was induced by an element(s) in amino acids 334–342. Basal internalization in JRT3 cells was increased by an element in amino acids 322–334. SDF‐1alpha induced internalization was similarly regulated by the TCR. Research was supported by the Summer Undergraduate Research Fellowship at Mayo Clinic and Mayo Graduate School.