Alternative titles; symbols
HGNC Approved Gene Symbol: LSP1
Cytogenetic location: 11p15.5 Genomic coordinates (GRCh38): 11:1,853,084-1,892,263 (from NCBI)
Signal transduction in B lymphocytes following antigen binding to a membrane-associated immunoglobulin complex initiates a diverse array of intracellular events. To define genes participating in these events, May et al. (1993) and others used various cDNA cloning strategies to identify genes preferentially expressed in B lymphocytes. One gene, variously named LSP1 and pp52, exhibited a number of properties supporting a possible role in B-cell signaling pathways. The gene codes for a 52-kD phosphoprotein expressed only in transformed and untransformed B cells, thymocytes, and untransformed T-cell lines.
Li et al. (1995) found that LSP1 is expressed in all human leukocytes, and that the expression is upregulated during monocytic and granulocytic differentiation.
Thompson et al. (1996) showed that tissue-specific alternative splicing produced 2 different Lsp1 transcripts in mouse. In lymphocytes, exon 1L is used, while exon 1S is used in stromal cells. Both the 5-prime untranslated regions and amino acid sequences of the alternative exons are distinct and are apparently transcribed using different tissue-specific promoters.
May et al. (1993) mapped the LSP1 gene to 11p15.5 by fluorescence in situ hybridization. They unexpectedly found that the human pp52 gene is 1 of 4 closely related loci. Two of the 4 loci harbored dysfunctional frameshift mutations or premature translation stop sites. These hybridized to 1q12 and 2p11.2. They were unable to map the fourth gene. May et al. (1993) pointed out that 11p15.5 is a location associated with karyotypic abnormalities in certain B-cell malignancies.
Easton et al. (2007) identified a T/C SNP (rs3817198) in the LSP1 gene that was significantly (p = 3 x 10(-9)) associated with familial breast cancer (114480) in a 3-stage genomewide association study of 22,848 cases from 22 studies. Easton et al. (2007) found that the allele was common in the U.K. population and thus unlikely to confer increased disease risk individually. However, in combination with other susceptibility alleles, the SNP may become clinically significant.
In a study of 9,442 BRCA1 (113705) and 5,665 BRCA2 (600185) mutation carriers from 33 study centers, Antoniou et al. (2009) found that the minor allele (C) of the SNP rs3817198 in LSP1 on chromosome 11p15.5 was associated with increased breast cancer risk only for BRCA2 mutation carriers (P trend = 2.8 x 10(-4)).
Liu et al. (2005) noted that LSP1 is an intracellular Ca(2+)- and F-actin (see 102610)-binding protein and a major substrate of MAPKAPK2 (602006) in the p38 MAPK (MAPK14; 600289) pathway. Using intravital microscopy, they demonstrated that Lsp1 -/- mice had impaired neutrophil extravasation in response to Tnf (191160), Il1b (147720), and Cxcl1 (155730), but no deficit in neutrophil rolling or adhesion. Transplantation experiments showed that wildtype leukocytes had a migration defect in Lsp1 -/- mice, whereas Lsp1 -/- neutrophils extravasated normally in wildtype mice. Vascular permeability to histamine was also reduced in Lsp1 -/- mice. Immunofluorescence microscopy and Western blot analysis showed that Lsp1 was present in wildtype but not Lsp1 -/- microvascular endothelial cells, and cultured human endothelial cells also expressed LSP1. Liu et al. (2005) proposed that LSP1 expressed in endothelium regulates neutrophil transendothelial migration.
Antoniou, A. C., Sinilnikova, O. M., McGuffog, L., Healey, S., Nevanlinna, H., Heikkinen, T., Simard, J., Spurdle, A. B., Beesley, J., Chen, X., Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, Neuhausen, S. L., and 131 others. Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers. Hum. Molec. Genet. 18: 4442-4456, 2009. [PubMed: 19656774] [Full Text: https://doi.org/10.1093/hmg/ddp372]
Easton, D. F., Pooley, K. A., Dunning, A. M., Pharoah, P. D. P., Thompson, D., Ballinger, D. G., Struewing, J. P., Morrison, J., Field, H., Luben, R., Wareham, N., Ahmed, S., and 93 others. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447: 1087-1093, 2007. [PubMed: 17529967] [Full Text: https://doi.org/10.1038/nature05887]
Li, Y., Guerrero, A., Howard, T. H. The actin-binding protein, lymphocyte-specific protein 1, is expressed in human leukocytes and human myeloid and lymphoid cell lines. J. Immun. 155: 3563-3569, 1995. [PubMed: 7561054]
Liu, L., Cara, D. C., Kaur, J., Raharjo, E., Mullaly, S. C., Jongstra-Bilen, J., Jongstra, J., Kubes, P. LSP1 is an endothelial gatekeeper of leukocyte transendothelial migration. J. Exp. Med. 201: 409-418, 2005. [PubMed: 15684321] [Full Text: https://doi.org/10.1084/jem.20040830]
May, W., Korenberg, J. R., Chen, X. N., Lunsford, L., Wood, W. J., Thompson, A., Wall, R., Denny, C. T. Human lymphocyte-specific pp52 gene is a member of a highly conserved dispersed family. Genomics 15: 515-520, 1993. [PubMed: 8468046] [Full Text: https://doi.org/10.1006/geno.1993.1102]
Thompson, A. A., Omori, S. A., Gilly, M. J., May, W., Gordon, M. S., Wood, W. J., Jr., Miyoshi, E., Malone, C. S., Gimble, J., Denny, C. T., Wall, R. Alternatively spliced exons encode the tissue-specific 5-prime termini of leukocyte pp52 and stromal cell S37 mRNA isoforms. Genomics 32: 352-357, 1996. [PubMed: 8838798] [Full Text: https://doi.org/10.1006/geno.1996.0129]