Disease relevance of LCP1

• This finding also suggests that the LCP1 locus is linked to the retinoblastoma gene, which is assigned to the same chromosomal region and closely linked to the ESD locus [1].
• An expanded survey of normal cell types and 50 tumor cell lines, demonstrated that 68% of carcinomas and 53% of other solid tumors of nonepithelial origin exhibited L-plastin expression, whereas the normal stem cell progenitors did not [2].
• Fibrosarcomas (n = 4), ovarian carcinomas (n = 9), breast carcinomas (n = 4), and choriocarcinomas (n = 2) combined exhibited the highest frequency and levels of L-plastin expression (95% frequency) [2].
• L-plastin, a gene that codes for an actin-bundling protein, is upregulated in the metastatic colon cancer cell line SW620, when compared to its premetastatic counterpart SW480 [3].
• A survey of SV40-transformed human fibroblasts and human sarcoma and carcinoma cell types demonstrated that the L-plastin gene was activated at widely varying degrees in nearly all human cancer cells [4].

Psychiatry related information on LCP1

• METHOD: They measured the number of lymphocyte cytosolic glucocorticoid receptors and plasma cortisol concentrations in 15 consecutively admitted male combat Vietnam veterans with PTSD and in a normal comparison group of 11 subjects [5].

High impact information on LCP1

• L-plastin remains associated with microfilaments while T-plastin is almost completely extracted after treatment of the cells with non-ionic detergent [6].
• To learn more about the biological significance of their tissue specificity, we have overproduced the T- and L-plastin isoforms in a fibroblast-like cell line, CV-1, and in a polarized epithelial cell line, LLC-PK1 [6].
• L-plastin is found in only normal or transformed leukocytes where it becomes phosphorylated in response to IL 1 or phorbol myristate acetate [7].
• L-plastin-derived peptides that included the phosphorylation site (Ser-5) rapidly induced leukocyte integrin-mediated adhesion when introduced into the cytosol of freshly isolated primary human PMN and monocytes [8].
• Because inflammatory stimuli that activate integrin-mediated adhesion in human polymorphonuclear neutrophils (PMN) and monocytes cause phosphorylation of the actin-bundling protein L-plastin, we tested whether L-plastin phosphorylation was involved in integrin activation [8].

Chemical compound and disease context of LCP1

• In PC-3 prostate cancer cells, cooperation among L-plastin AREs was still evident although individually they had moderate levels of testosterone/AR responsiveness [9].
• Taken together, these results suggest that the expression of L-plastin in prostatic epithelial cells is linked to the malignant state and that, once expressed in carcinomas, its expression is regulated by steroid hormone receptors [10].

Biological context of LCP1

• The genetic linkage of the loci for lymphocyte cytosol polypeptide with molecular weight of 64,000 (LCP1) and esterase (ESD) were examined by two-dimensional gel electrophoresis using blood from four informative families [1].
• In addition, the phenotype of LCP1 derived from the father was not expressed in the lymphocyte proteins from the patient [11].
• A case report of a patient with retinoblastoma and chromosome 13q deletion: assignment of a new gene (gene for LCP1) on human chromosome 13 [11].
• Use of monoclonal antibodies that distinguished the two Fc receptors demonstrated that FcgammaRII ligation was 100-fold more potent at signaling L-plastin phosphorylation than occupancy of FcgammaRIIIB [12].
• We conclude that efficient FcgammaRII-mediated phosphorylation of L-plastin requires cell adhesion but does not require IgG-induced rearrangements of the actin cytoskeleton [12].

Anatomical context of LCP1

• Evidence for the close linkage between lymphocyte cytosol polypeptide with molecular weight of 64,000 (LCP1) and esterase D [1].
• In contrast, L-plastin expression was restricted to the spleen and other lymph node-containing organs, while T-plastin was expressed in a variety of organs, including muscle, brain, uterus, and esophagus [13].
• Expression of the L-plastin isoform appears to be restricted to replicating blood cells, and the two T-plastin isoforms appear to be restricted to replicating cells of solid tissues [14].
• L-Plastin is a calcium-regulated actin bundling protein expressed in leukocytes and some transformed cells, which is phosphorylated on serine in response to several different leukocyte-activating stimuli [12].
• FcgammaRII-mediated adhesion and phagocytosis induce L-plastin phosphorylation in human neutrophils [12].

Associations of LCP1 with chemical compounds

• Adhesion to immune complexes caused L-plastin to localize to podosomes, since it colocalized with actin to discrete, punctate Triton X-100-insoluble sites on the adherent neutrophil surface in a pattern indistinguishable from vinculin and alpha-actinin [12].
• We discovered that the gene encoding L-plastin contains potential estrogen and progesterone response elements upstream from its promoter, suggesting that L-plastin expression is subject to ovarian steroid regulation [15].
• Stimulation of L-plastin synthesis by E2 and MPA was also evident by examination of protein synthesis using high-resolution two-dimensional gel electrophoresis and Western blotting [15].
• Primary SC, which synthesized estrogen receptor and progesterone receptor mRNA transcripts, dramatically elevated L-plastin transcript synthesis in response to treatment with estradiol (E2) and medroxyprogesterone acetate (MPA) [15].
• Immune complex-induced integrin activation and L-plastin phosphorylation require protein kinase A [16].

Physical interactions of LCP1

• Our recent finding that grancalcin interacts with L-plastin, a protein known to have actin bundling activity, suggests that grancalcin may play a role in regulation of adherence and migration of neutrophils [17].
• ALP bound to the actin-bundling protein L-plastin and down-modulated filamentous actin assembly in response to stimulation with IgG-coated latex beads in granulocytes [18].
• The biochemical characteristics (m.w. and isoelectric point) of p67 are identical with those of the actin binding protein L-plastin (Fimbrin), a cytoplasmic protein that contains two Ca2+ binding sites and a calmodulin binding domain [19].

Regulatory relationships of LCP1

• These data suggest a model in which plastin phosphorylation and localization to the actin cytoskeleton can act as two distinct mechanisms regulating L-plastin functions in neutrophils adherent to immune complexes [12].
• We now obtained evidence that L-plastin gene expression was positively regulated by testosterone in androgen receptor (AR)-positive prostate and breast cancer cells [9].
• N-Formyl peptide receptor subtypes in human neutrophils activate L-plastin phosphorylation through different signal transduction intermediates [20].

Other interactions of LCP1

• Low birthweight infants (< or =2500 g) received LCP1 formula (n = 16; 0.31% 18:3 omega6, 0.17% 20:5 omega3 and 0.20% 22:6 omega3) or LCP2 formula (n = 13; 0.32% 18:3 omega6, 0.34% 20:5 omega3 and 0.43% 22:6 omega3) [21].
• This result indicates that the gene for LCP1 is closely linked to the ESD locus, which is assigned to the chromosomal region 13q14.11 [1].
• This was substantiated by co-immunoprecipitation of grancalcin by anti-L-plastin antibodies and vice versa [22].
• Depletion of intracellular calcium did not affect FcgammaRII-activated L-plastin phosphorylation, demonstrating that any potential regulation of plastin function by calcium did not affect its phosphorylation [12].
• The leukocyte protein L-plastin induces proliferation, invasion and loss of E-cadherin expression in colon cancer cells [3].

Analytical, diagnostic and therapeutic context of LCP1

• By affinity chromatography of solubilized human neutrophils on immobilized grancalcin, L-plastin, a leukocyte-specific actin-bundling protein, was found to interact with grancalcin in a negative Ca(2+)-dependent manner [22].
• Calculated mature protein molecular masses are 23386 (LCP1), 29093 (LCP2) and 23255 (LCP3) Sequence alignments show that the lobster enzymes are more similar to L (55-62% identity) than H (42-44%) or B (22-24%) cathepsins [23].
• Sequence analysis and expression of a mRNA for a larval-specific cuticular protein, LCP1, from Helicoverpa armigera [24].
• The low level activation of the L-plastin gene, detectable only by RT-PCR, was confirmed by using the recombinant human L-plastin promoter to select "L-plastin positive" clonal subpopulations from these RT-PCR-positive cell lines [25].
• A comparison between principal component regression (PCR) and two partial least squares (PLS) algorithms, PLS-1 and PLS-2, with different pre-processing methodologies was made [26].

References