Biomedical subjects

A Veillette

Publications and source records attributed to A Veillette.

82 records · Page 5Linked to original sources

PubMed1989

Coordinate alteration of pp60c-src abundance and c-src RNA expression in human neuroblastoma variants.

We examined the expression, abundance, and protein kinase activity of pp60c-src in two different pairs of genetically indistinguishable cloned human neuroblastoma cell variants which display altered phenotypes as the result of conversion from a neuronal to a non-neuronal phenotype. The results demonstrate that cells which exhibit the neuroblastic (N-type) phenotype possess high levels of pp60c-src protein and that one of the two N-type cell lines is capable of expressing the neuronal-specific isoenzyme of pp60c-src. In contrast, cells which display the substrate-adherent (S-type) phenotype have low levels of pp60c-src protein and express exclusively the non-neuronal isoenzyme of pp60c-src. In all cells examined the abundance of pp60c-src was found to be proportional to the steady-state level of c-src RNA. In each case the protein kinase activity of pp60c-src was found to be proportional to the abundance of the protein and independent of the ratio of neuronal to non-neuronal species of pp60c-src.

Humans↗

PubMed1989

Alterations in the expression of pp60c-src and p56lck associated with butyrate-induced differentiation of human colon carcinoma cells.

The effects of butyrate-mediated differentiation of human colon carcinoma cells on the expression of src-related tyrosine protein kinases were analyzed. The results demonstrate that treatment of a variety of colon carcinoma cell lines with 2 mM sodium butyrate resulted in diminished population doubling rates, altered morphology, decreased anchorage-independent growth, and increased expression of colon epithelial differentiation marker enzymes such as alkaline phosphatase. In butyrate-treated cells, significantly diminished protein kinase activities and abundance of pp60c-src and p56lck were found to parallel the butyrate-induced phenotypic alterations. For the lck gene, the decreased levels in p56lck abundance were found to coincide with diminished levels of steady-state lck mRNAs. In contrast, treatments which arrested the growth of the colon carcinoma cells without inducing differentiation had no effect on the level of expression of these proteins. Furthermore, colon carcinoma cell lines which were found to be resistant to butyrate-induced differentiation showed no change in the kinase activity or abundance of either protein following butyrate treatment. These results indicate that the expression of several src-related kinases in human colon carcinoma can be influenced by the differentiation state of the cells.

Alkaline Phosphatase↗

PubMed1989

CD4 and p56lck can stably associate when co-expressed in NIH3T3 cells.

The CD4 T-cell surface antigen and the lymphocyte-specific tyrosine-protein kinase p56lck form a stable noncovalent complex in CD4+ T-lymphocytes. In this report, we demonstrate that these two gene products can also associate when co-expressed in NIH3T3 fibroblasts, therefore implying that other lymphoid specific components are not required for the CD4-lck interaction. These results also suggest that co-expression of CD4 and p56lck in non-lymphoid cells may prove to be a useful model system for the analysis of structural and possibly functional CD4-lck interactions.

Animals↗

PubMed1988

The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck.

The CD4 and CD8 T cell antigens are thought to transduce an independent signal during the process of T cell activation. We report our evaluation of the possible involvement of the lymphocyte-specific tyrosine kinase p56lck in these transduction pathways. Our data demonstrate that p56lck is specifically modulated with either CD4 or CD8 following antibody-mediated cross-linking of these molecules and that a large fraction of the total cellular lck protein can be coimmunoprecipitated with these surface glycoproteins. These results suggest that p56lck is functionally and physically associated with CD4/CD8 in normal murine T lymphocytes and support the concept that an independent signal is transduced by the interaction of these surface molecules with major histocompatibility complex determinants.

Animals↗

PubMed1988

Alterations of the lymphocyte-specific protein tyrosine kinase (p56lck) during T-cell activation.

The lymphocyte-specific tyrosine protein kinase p56lck is abundantly expressed in L3T4+ (CD4+) and Lyt-2+ (CD8+) T-lymphocytes, where it is predominantly phosphorylated in vivo on the carboxy-terminal tyrosine residue 505 (Y-505). Upon exposure to activating signals (mitogenic lectins, antibodies to the T-cell receptor), the p56lck expressed in normal cloned murine T-cells is modified into a product which migrates at approximately 59 kilodaltons on sodium dodecyl sulfate-polyacrylamide gels and which possesses several amino-terminal serine phosphorylations. The changes in both mobility and amino-terminal phosphorylation can be reproduced by known activators of protein kinase C (4 alpha-phorbol 12 beta-myristate, dioctanoylglycerol), suggesting that this signal transduction pathway (or related pathways) mediates at least part of these events. Interestingly, agents raising intracellular calcium (such as A23187) cause the appearance of several of these amino-terminal phosphorylation changes but do not cause the pronounced shift in electrophoretic mobility. These data suggest that at least two serine kinase systems are implicated in the alterations of p56lck associated with T-cell activation and that the lck gene product plays a critical role in normal T-cell physiology.

Animals↗

PubMed1988

Post-translational alterations of the tyrosine kinase p56lck in response to activators of protein kinase C.

We have found in different human cells of lymphoid and non-lymphoid origin that the 56 kilodalton (kDa) lck protein is rapidly converted to a product migrating at approximately 60 kDa (designated p60lck) in response to the phorbol ester 4 alpha-phorbol 12 beta-myristate (PMA) as well as the diacylglycerol analogue 1,2-dioctanoyl-sn-glycerol (diC8). This conversion is associated with an increase in serine phosphorylation within the amino-terminal 18 kDa portion of the lck protein. The serine phosphorylation modification and diminished electrophoretic mobility of the lck protein appear to be completely reversible within 60 min following treatment with diC8. The changes in p56lck phosphorylation and gel mobility in response to activators of protein kinase C are also associated with a small but reproducible decrease in the ability of the lck protein to be phosphorylated in immune complex kinase assays. While these alterations of the lck gene product may play an important role in antigen-mediated activation of T-lymphocytes, we demonstrated that they can also be induced independently of T-cell activation suggesting that they are not necessarily implicative of this process.

Diglycerides↗

PubMed1987

Activation of pp60c-src protein kinase activity in human colon carcinoma.

The tyrosine-specific protein kinase activity of pp60c-src molecules obtained from human colon carcinoma tissues and tumor-derived cell lines was found to be elevated over that from normal colon tissues or cultures of normal colon mucosal cells. The elevated pp60c-src protein kinase activity in tumor tissues and in cultured colon carcinoma cells does not appear to result solely from an increase in the abundance of the c-src-encoded protein, suggesting that the specific activity of the pp60c-src tyrosine phosphotransferase is enhanced. These results raise the possibility that activation of the pp60c-src protein kinase may contribute to the genesis of human colon tumors.

Cell Line↗

PubMed1987

Analysis of pp60c-src in human colon carcinoma and normal human colon mucosal cells.

The tyrosine-specific protein kinase activity of pp60c-src molecules obtained from RIPA buffer lysates of human colon tumor-derived cell lines is elevated over that found in lysates from normal human colon mucosa cells. The elevation of pp60c-src kinase activity in the lysates of the cultured colon tumor cells does not appear to be the result of pp60c-src overexpression suggesting that the specific activity of the pp60c-src phosphotransferase may be enhanced. Cell-free translation of c-src mRNA from colon tumor cells and normal colon mucosa cells yielded pp60c-src molecules with similar levels of in vitro protein kinase activity suggesting that pp60c-src kinase activity in these cells may be regulated differently at a post-translational level. Analysis of pp60c-src molecules from normal colon and colon carcinoma cells revealed that they possessed indistinguishable sites and quantities of phosphorylated serine and tyrosine residues and were not detectably complexed with other cellular proteins. The activation of pp60c-src kinase activity in the colon tumor cells is associated with an apparent increase in the turnover rate of tyrosine-phosphates within the carboxyl terminal portion of the pp60c-src molecules from these tumor derived cell lines.

Colon↗

PubMed1986

17 beta-estradiol regulates and v-Ha-ras transfection constitutively enhances MCF7 breast cancer cell interactions with basement membrane.

The interaction of a line of human breast carcinoma cells (MCF7) with basement membrane components, particularly laminin, was altered by exposure of the cells to estrogen as well as by transfection of the cells with the v-Ha-ras oncogene. In both cases, the cells show a greater ability to attach to a laminin substrate, to migrate to laminin, to grow in the presence of a basement membrane matrix, and to cross barriers of reconstituted basement membrane. These responses were associated with an increase in the expression of laminin receptors. It is postulated that the increase in the invasive behavior of the cells treated with estrogen or transfected with v-Ha-ras is related to the increased number of laminin receptors and their interaction with laminin. Estrogen had no discernible effect on the v-Ha-ras transfected cells. It appears that in the MCF7 cells, the malignant phenotype is under hormonal control and that this control is bypassed after v-Ha-ras transfection.

Basement Membrane↗

PubMedDate not supplied

Expression of the lck tyrosine kinase gene in human colon carcinoma and other non-lymphoid human tumor cell lines.

The tyrosine kinase p56lck is felt to be expressed solely in cells and tissues of lymphoid lineage. We have observed in the particulate fractions of colon carcinoma cells the presence of a 56 kilodalton (kD) alkali resistant phosphoprotein containing phosphotyrosine. Further analysis revealed that the partial proteolytic cleavage pattern of this protein is analogous to that of the lck gene product found in murine and human T-cells. We have confirmed by cDNA cloning that lck RNA is also expressed in these cells proportionally to the amount of p56lck found in membrane preparations. Additional analysis demonstrated that lck RNA is frequently expressed in certain non-lymphoid tumor cell lines such as cell lines derived from colon carcinomas and carcinomas of the lung. Interestingly, higher levels of lck expression were found in human tumor cell lines derived from metastatic tumor sites when compared to those derived from primary tumors. These observations raise the possibility that the lck gene product may be involved in progression of some non-lymphoid human tumors.

Adenocarcinoma↗