Disease relevance of LASP1

• Rapid amplification of cDNA ends (RACE) revealed an in-frame fusion of MLL to LASP1, a gene that is amplified and overexpressed in breast cancer [1].
• The human LASP1 gene is fused to MLL in an acute myeloid leukemia with t(11;17)(q23;q21) [1].
• Overexpression of LASP-1 mediates migration and proliferation of human ovarian cancer cells and influences zyxin localisation [2].
• In this study, we show that MLN 50, which is expressed at a basal level in normal tissues, is overexpressed in 8% of human breast carcinomas most often together with c-erbB-2 [3].
• MLN 50 was previously identified in a cDNA library of breast cancer metastasis [3].

High impact information on LASP1

• Cotransfection of PtK-2 cells with LASP and cGK confirmed phosphorylation of LASP in vivo [4].
• Taken together, these data suggest that phosphorylation of LASP by cGK and cAK may be involved in cytoskeletal organization and cell motility [4].
• In the present study we identified the LIM and SH3 domain protein (LASP) that was recently cloned from human breast cancer cells (Tomasetto, C., Regnier, C., Moog-Lutz, C., Mattei, M. G., Chenard, M. P., Liderau, R., Basset, P., and Rio, M. C. (1995) Genomics 28, 367-376) as a novel substrate of cGK in human platelets [4].
• LASP is an actin-binding protein, and the phospho-LASP-mimicking mutant S146D showed reduced binding affinity for F-actin in cosedimentation experiments [4].
• Studies with human LASP mutants identified serine 146 as a specific phosphorylation site for cGK and cAK in vivo [4].

Biological context of LASP1

• Here, we identified and characterized a novel LASP1-related gene, LASP2, by using bioinformatics [5].
• The LASP1 gene was localized to a pair of microchromosomes and the LASP2 gene was localized to chromosome 2p3.1, indicating that the chromosomal locations of the LASP1 and LASP2 genes are highly conserved between chicken and human [6].
• Our results have yielded many novel and interesting genes exhibiting differential expression in lactating mammary tissue, including oncogenes (VAV3, C-myc), mediators of apoptosis (Caspase 8), and cell cycle regulators (LASP1) [7].
• Microsequencing and site-directed mutagenesis localized the major in vivo and in vitro PKA-dependent phosphorylation sites in rabbit lasp-1 to S(99) and S(146) [8].
• Transfection of lasp-1 cDNA encoding for alanine substitutions at S(99) and S(146), into parietal cells appeared to suppress the cAMP-dependent translocation of lasp-1 to the intracellular canalicular region [8].

Anatomical context of LASP1

• The localization of lasp-1 to these subcellular regions under a range of experimental conditions and the phosphorylation-dependent regulation of this protein in F-actin rich epithelial cells suggests an integral and possibly cell-specific role in modulating cytoskeletal/membrane-based cellular activities [8].
• In gastric fibroblasts, exposure to the protein kinase C activator, PMA, was correlated with the translocation of lasp-1 into newly formed F-actin-rich lamellipodial extensions and nascent focal complexes [8].
• In the gastric parietal cell, cAMP-dependent phosphorylation induces the partial translocation of lasp-1 to the apically directed F-actin-rich canalicular membrane, which is the site of active HCl secretion [8].
• In addition, we provide evidence that lasp-1 is concentrated within focal complexes as well as in the leading edges of lamellipodia and the tips of filopodia in non-transformed gastric fibroblasts [8].
• Lasp-1 has been identified as a signaling molecule that is phosphorylated upon elevation of [cAMP]i in pancreas, intestine and gastric mucosa and is selectively expressed in cells within epithelial tissues [8].

Associations of LASP1 with chemical compounds

• LASP2 and LASP1 were the LASP family proteins consisting of LIM domain, Nebulin repeat, and SH3 domain [5].
• Phosphorylation of mouse LASP-1 on threonine 156 by cAMP- and cGMP-dependent protein kinase [9].

Physical interactions of LASP1

• LASP-1 silencing is accompanied by a reduced binding of the LASP-1-binding partner zyxin to focal contacts without changes in actin stress fibre and microtubule organisation or focal adhesion morphology as observed by immunofluorescence [2].

Other interactions of LASP1

• Lasp-1 is an unusual modular protein that contains an N-terminal LIM domain, a C-terminal SH3 domain and two internal nebulin repeats [8].
• The data provide evidence for an essential role of LASP-1 in tumor cell growth and migration, possibly by influencing the localization of zyxin [10].
• The family members now include nebulin, nebulette, N-RAP, LASP-1, and LIM-nebulette [11].

Analytical, diagnostic and therapeutic context of LASP1

• We determined the chromosomal locations of the LASP1 and LASP2 genes in chicken by fluorescence in situ hybridization [6].
• Immunoblotting of LASP-1 in various mouse and human tissues detected a similar prominent expression in non-muscle tissue [9].
• Combined Northern and Western blot analyses indicate that pp40/lasp-1 is widely expressed (through a single 3.3-kb message) not only in epithelial tissues but also in muscle and brain [12].

References