Leupaxin is serine phosphorylated and recruited to the immunological synapse upon TCR engagement in cytotoxic T lymphocytes (CTL)

Autor: Shugang Yao, Hanne Ostergaard
Rok vydání: 2017
Předmět:
Zdroj: The Journal of Immunology. 198:52.28-52.28
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.198.supp.52.28
Popis: Background Leupaxin is a member of paxillin family proteins that function as adaptor proteins in integrin signaling. Compared to other members, leupaxin is mainly expressed in leukocytes. However, the role of leupaxin in T cells is unknown. Results Leupaxin has been shown to be tyrosine phosphorylated in cells including tumor cells, fibroblasts and B cells. However we detected no leupaxin tyrosine phosphorylation in T cells. Instead, leupaxin showed mobility shift in response to TCR signaling. We demonstrated that the mobility shift was caused by serine phosphorylation and was ERK dependent. Although leupaxin is downstream of integrin receptors, LFA-1 stimulation did not induce leupaxin phosphorylation. Several potentially phosphorylated residues were mutated into alanine individually. When Ser54 was mutated, leupaxin no longer showed mobility shift, suggesting that leupaxin is phosphorylated at Ser54. Leupaxin was recruited to the immunological synapse and colocalized with LFA-1. Leupaxin has N-terminal leucine-aspartic acid (LD) domains and C-terminal LIM domains that contain four double zinc finger motifs. The LIM domains were dispensable for leupaxin localization at the contact zone. Leupaxin failed to be recruited to the immunological synapse after deleting LD2–4 domains, suggesting the importance of LD2–4 domains for the recruitment. Conclusions Leupaxin is not tyrosine phosphorylated but serine phosphorylated at Ser54 in response to TCR engagement. Leupaxin is recruited to the immunological synapse through LD2–4 domains. Studies are underway to determine the contribution of leupaxin to CTL adhesion, polarization and degranulation.
Databáze: OpenAIRE
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