Identification of novel isoforms of mouse L-selectin with different carboxyl-terminal tails.
The leukocyte adhesion molecule L-selectin mediates the recruitment of lymphocytes to secondary lymphoid organs and is involved in the accumulation of neutrophils at sites of inflammation. In this study, we report the identification of novel isoforms of the mouse L-selectin gene, termed L-selectin-v1 and L-selectin-v2. Sequence analysis revealed that these isoforms are generated by alternative splicing: the L-selectin-v2 transcript includes a previously unknown exon of 100 bp located between the 7th and 8th exons of the mouse L-selectin gene, while the L-selectin-v1 transcript contains the first 49-bp sequence of this new exon. The insertion of each new sequence adds a downstream reading frame, giving rise to predicted proteins that differ in their carboxyl-terminal tails. These splice variants were found in cells that express conventional L-selectin, termed L-selectin-c, including B and T lymphocytes and granulocytes. Functionally, like L-selectin-c, both L-selectin-v1 and L-selectin-v2 expressed in cultured cells underwent phorbol ester-induced shedding, although L-selectin-v1 and L-selectin-v2 were shed to a greater and lesser degree, respectively, than L-selectin-c. Under flow conditions, both L-selectin-v1 and L-selectin-v2 mediated faster cell rolling than did L-selectin-c. In addition, ligation of L-selectin-c and L-selectin-v1, but not L-selectin-v2, induced p38 mitogen-activated protein kinase phosphorylation. These results suggest that alternative splicing is one mechanism for generating functional diversity in L-selectin.
Furukawa
Yuko
Y
The 21st Century Center of Excellence Program, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Umemoto
Eiji
E
Jang
Myoung Ho
MH
Tohya
Kazuo
K
Miyasaka
Masayuki
M
Hirata
Takako
T
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D019041:L-Selectin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D020033:Protein Isoforms; D012333:RNA, Messenger; D019041:L-Selectin; D048051:p38 Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate