九源奖学金

Selectins, a Family of cell adhesion molecules, bind to sialyated and fucosylated carbohydrates, such as sialyl Lewis*(SLe*) and its derivatives, as their minimal recognition motif. Here we report that P-selectin bound to human malignant melanoma A375 cells and mediated their adhesion under flow. However，probing with specific Ab failed to detect to any apparent expression of SLe*.This finding was bolstered by reduced expression of α-1,3-fucosyltransferase VⅡmRNA and by absence of the cell surface expression of P-selectin glycoprotein ligand-1. Instead, they expressed heparan sulfate-like proteglycans on their cell surfaces. Treatment with β-D-xyloside (a proteoglycan biosynthesis inhibitor) or heparinases could reduce the binding of these cells to P-selectin. In the competition assays, heparin, but not other proteglycans, could abolish the P-selectin recognition. Further, we found that P-selectin could bind specifically to human tongue squamous cancer Tca-8113 cells, which had negative staining of SLe* but positive staining of heparan sulfates. Both β-D-xyloside and heparinases could reduce the binding of P-selectin to Tca-8113 cells. Our results thus indicate that heparan sulfate-like proteoglycans can mediate adhesion of certain types of non-blood borne. "epithelial-like" human cancer cells to P-selectin.

作者：马衍青（中科院上海生化和细胞研究所，分子细胞生物学博士，导师：耿建国教授）

5、c-Crk, a Substrate of Insulin-like Growth Factor-1 Receptor Tyrosine Kinase, Function as an Early Signal Mediator in the Adipocyte Differentiation Process（发表刊物：The Journal of Biological Chemistry（2001），Vol.275.： 34344-34352.）

Differentiation of 3T3-L1.preadipocytes into adipocytes is induced by a combination of inducers, including a glucocorticoid, an agent that elevates cellular cAMP, and a ligand of the insulin-like growth factor-1 receptor. Previous studies have implicated protein-tyrosine phosphatase (PTPase) HA2, a homologue of PTPase 1B, in the signaling cascade initiated by the differentiation inducers. Vanadate, a potent PTPase inhibitor, blocks adipocyte differentiation at an early stage in the program, but has no effect on the mitotic clonal expansion required for differentiation. Exposure of preadipocytes to vanadate along with the inducing agents led to the accumulation of pp35, a phosphotyrosyl protein that is a substrate for PTPase HA2. pp35 was purified to homogeneity and shown by amino acid sequence and mass analyses of tryptic peptides to be c-Crk, a known cytoplasmic target of the insulin-like growth factor-1 receptor tyrosine kinase. Transfection of 3T3-L1 preadipocytes with a c-Crk antisense RNA expression vector markedly reduced c-Crk levels and prevented differentiation into adipocytes. Studies with C3G, a protein that binds to the SH3 domain in c-Crk, showed that phosphorylation of c-Crk rendered the SH3 domain inaccessible to C3G. Taken together, these findings indicate that locking c-Crk in the phosphorylated state with vanadate prevents its participation in the signaling system that initiates adipocyte differentiation.

作者：翟波（中国科学院上海生物化学与细胞生物学研究所，生物化学博士，导师：廖侃教授）

6、Cloning and characterization of siglec-10, a novel sialic acid binding member of the Ig superfamily, from human dendritic cells.（发表刊物：J Biol Chem 2001；276：28106-28112）

The Siglecs (sialic acid-binding Ig-like lectins) are a subfamily of I-type lectins, Which specifically recognize sialic acids. Nine members of the family have been identified thus far. We have obtained a novel cDNA clone from a human dendritic cell cDNA library encoding a protein with sequence and structural features of the Siglec family, hence designated as Siglec-10. The full length Siglec-10 cDNA encodes a type 1 transmembrane protein containing four extracellular immunoglobulinlike domains, a transmembrane region, and a cytoplasmic tail with two classical immunoreceptor tyrosinebased inhibitory motifs. The N-terminal V-set Ig domain has most of the amino acid residues typical of the Siglecs. Siglec-10 shows the closet homology to Siglec-5 and Siglec-3/CD33. Various cells and cell and cell lines including monocytes and dendritic cells espress Siglec-10. High levels of mRNA expression were seen in peripheral blood leukocytes, spleen, and liver. When expressed on COS-7 cells, Siglec-10 was able to bind human red blood cells and soluble sialoglycoconjugates in a sialic acid-dependent manner. The identification of Siglec-10 as a new Siglec family member and its expression profile, together with its sialic acid-dependent binding capacity, suggest that it may be involved in cell-cell recognition by interacting with sialylated ligands expressed on specific cell populations.

作者：李楠（第二军医大学基础部免疫学教研室，基础免疫学博士，导师：曹雪涛教授）

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