Biological data extinction.
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Computational Biology↗
Biomedical subjects
Peter Li
Publications and source records attributed to Peter Li.
Rat Muc4 (sialomucin complex) reduces binding of anti-ErbB2 antibodies to tumor cell surfaces, a potential mechanism for herceptin resistance.
Muc4 (also called sialomucin complex), the rat homolog of human MUC4, is a heterodimeric glycoprotein complex that consists of a peripheral O-glycosylated mucin subunit, ASGP-1, tightly but noncovalently linked to a N-glycosylated transmembrane subunit, ASGP-2. The complex is expressed in a number of normal, vulnerable epithelial tissues, including mammary gland, uterus, colon, cornea and trachea. Muc4/SMC is also overexpressed or aberrantly expressed on a number of human tumors including breast tumors. Overexpression of Muc4/SMC has been shown to block cell-cell and cell-matrix interactions, protect tumor cells from immune surveillance and promote metastasis. In addition, as a ligand for ErbB2, Muc4/SMC can potentiate phosphorylation of ErbB2 and potentially alter signals generated from this receptor. Using A375 human melanoma cells and MCF7 human breast adenocarcinoma cells stably transfected with tetracycline regulatable Muc4, we have investigated whether overexpression of Muc4/SMC can repress antibody binding to cell surface-expressed ErbB2. Overexpression of Muc4/SMC does not affect the level of ErbB2 expression in either cell line, but it does reduce binding of a number of anti-ErbB2 antibodies, including Herceptin. Interestingly, overexpression of ErbB2 does not block binding of other unrelated antibodies of the same isotype, suggesting that the reduction in ErbB2 antibody binding is due to complex formation of Muc4/SMC and ErbB2. Furthermore, capping of Muc4/SMC with anti-Muc4/SMC antibodies reduces antibody binding to ErbB2 instead of increasing binding, again suggesting that reduced antibody binding to ErbB2 is due to steric hindrance from complex formation of Muc4/SMC and ErbB2. Thus, overexpression of Muc4/SMC on tumor cells may have both prognostic and therapeutic relevance.
Adenocarcinoma↗
The Celera Discovery System.
The Celera Discovery System (CDS) is a web-accessible research workbench for mining genomic and related biological information. Users have access to the human and mouse genome sequences with annotation presented in summary form in BioMolecule Reports for genes, transcripts and proteins. Over 40 additional databases are available, including sequence, mapping, mutation, genetic variation, mRNA expression, protein structure, motif and classification data. Data are accessible by browsing reports, through a variety of interactive graphical viewers, and by advanced query capability provided by the LION SRS search engine. A growing number of sequence analysis tools are available, including sequence similarity, pattern searching, multiple sequence alignment and Hidden Markov Model search. A user workspace keeps track of queries and analyses. CDS is widely used by the academic research community and requires a subscription for access. The system and academic pricing information are available at http://cds.celera.com.
Animals↗
ErbB2 and its ligand Muc4 (sialomucin complex) in rat lacrimal gland.
The lacrimal gland is an important source of components for the ocular tear fluid. Though mucins are not generally considered a product of the lacrimal gland, our results clearly show Muc4/SMC is produced by the gland in soluble and membrane forms. The secreted, soluble form is likely produced for the soluble phase of the ocular tear film. Analyses of ErbB2 and the Muc4/SMC-ErbB2 complex in the lacrimal gland suggest a second function for Muc4/SMC, a role in cell regulation through ErbB signaling. The nature of those signals and the cell functions they regulate will be subjects for future investigations.
Animals↗
A label-free optical technique for detecting small molecule interactions.
A novel approach for the label-free detection of molecular interactions is presented in which a colorimetric resonant grating is used as a surface binding platform. The grating, when illuminated with white light, is designed to reflect only a single wavelength. When molecules are attached to the surface, the reflected wavelength (color) is shifted due to the change of the optical path of light that is coupled into the grating. By linking receptor molecules to the grating surface, complementary binding molecules can be detected without the use of any kind of fluorescent probe or radioactive label. The detection technique is capable of detecting the addition and removal of small molecules as they interact with receptor molecules on the sensor surface or enzymes in the solution surrounding the sensor. Two assays are presented to exemplify the detection of small molecule interactions with the biosensor. First, an avidin receptor layer is used to detect 244 Da biotin binding. Second, a protease assay is performed in which a 136 Da p-nitroanilide (pNA) moeity is cleaved from an immobilized substrate. Because the sensor structure can be embedded in the plastic surfaces of microtiter plates or the glass surfaces of microarray slides, it is expected that this technology will be most useful in applications where large numbers of biomolecular interactions are measured in parallel, particularly when molecular labels will alter or inhibit the functionality of the molecules under study. Screening of pharmaceutical compound libraries with protein targets, and microarray screening of protein-protein interactions for proteomics are examples of applications that require the sensitivity and throughput afforded by this approach.
Avidin↗