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Dual acylation and lipid raft association of Src‐family protein tyrosine kinases are required for SDF‐1/CXCL12‐mediated chemotaxis in the Jurkat human T cell lymphoma cell line
Author(s) -
Zaman Sabiha N.,
Resek Mary E.,
Robbins Stephen M.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1007698
Subject(s) - jurkat cells , lipid raft , biology , chemotaxis , microbiology and biotechnology , tyrosine phosphorylation , signal transduction , tyrosine kinase , proto oncogene tyrosine protein kinase src , kinase , cell signaling , bruton's tyrosine kinase , t cell , immunology , receptor , immune system , biochemistry
Chemokines play pivotal roles in regulating a wide variety of biological processes by modulating cell migration and recruitment. Deregulation of chemokine signaling can alter cell recruitment, contributing to the pathogenic states associated with autoimmune disease, inflammatory disorders, and sepsis. During chemotaxis, lipid rafts and their resident signaling molecules have been demonstrated to partition to different parts of the cell. Herein, we investigated the role of lipid raft resident Src‐family kinases (SFK) in stromal cell‐derived factor 1/CXCL12‐mediated chemotaxis. We have shown that Lck‐deficient J. CaM 1.6 cells are defective in CXCL12‐mediated chemotaxis in contrast to their parental counterpart, Jurkat cells. Ectopic expression of the SFK hematopoietic cell kinase (Hck) in J. CaM 1.6 cells reconstituted CXCL12 responsiveness. The requirement of lipid raft association of SFK was assessed using both isoforms of Hck: the dually acylated p59 Hck isoform that is targeted to lipid rafts and the monoacylated p61 Hck isoform that is nonraft‐associated. We have shown using several gain and loss of acylation alleles that dual acylation of Hck was required for CXCL12‐mediated chemotaxis in J. CaM 1.6 cells. These results highlight the importance of the unique microenvironment provided by lipid rafts and their specific contribution in providing specificity to CXCL12 signaling.