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At least 163 records · Page 9Linked to original sources
PubMed1986

N-myc and c-src genes are differentially regulated in PCC7 embryonal carcinoma cells undergoing neuronal differentiation.

We examined the expression of N-myc, c-myc, and c-src in four embryonic carcinoma (EC) cell lines during different states of cell growth and following induction of in vitro differentiation. N-myc mRNA was detected in undifferentiated cells of four EC cell lines (PCC7, PCC3, PCC4, F9) neither of which showed N-myc gene amplification. No N-myc transcripts could be detected in mRNA prepared from a murine neuroblastoma cell line and from a murine fibroblast line. The level of N-myc mRNA decreased by 85% when PCC7 EC cells were induced by retinoic acid and cAMP treatment to form nerve-like cells. Six days after induction, the PCC7 cells changed into aggregates of neurofilament positive cells with massive neurite outgrowths. At this stage DNA replication had been reduced by more than 95%. The decreased N-myc expression in induced PCC7 cells was parallelled by 300-500% increase in c-src expression. Slowing of cell multiplication by serum starvation, on the other hand, did not affect the level of N-myc or c-src mRNA levels in PCC7 cells. C-myc was expressed in all EC lines except PCC7, which surprisingly did not express c-myc even at an exponential rate of proliferation. Chemical induction of F9 EC cells to form visceral endoderm or parietal endoderm resulted in markedly reduced (85%) levels of N-myc transcripts. A similar decline in c-myc expression was found in differentiated F9 cells. No c-src transcripts were detected in proliferating or differentiated F9 cells. These results suggest that N-myc may be expressed not only in neural development, but also in very early, undetermined embryonic cells. The activation of c-src expression when PCC7 EC cells differentiate into nerve-like cells shows that the pattern of proto-oncogene expression may change during a differentiation process, some proto-oncogenes increasing, others decreasing their representation in the mRNA pool.

Blood↗
PubMed1990

Subcloning and trial of expression of the protein kinase catalytic domain of RSV-src gene.

The gene of catalytic domain of the protein kinase of RSV-scr was cloned into the BamHI cloning site of translation vector pET-8c which containing T7 RNA polymerase promotor, and transformed BL21 (DE3) pLys S (Studier and Moffatt, 1986). The putative molecular weight of the protein was about 33 kd as evaluated on the basis of its nucleotide size showed the identical mobility in SDS-polyacrylamide gel electrophoresis. However, yield of protein production was not high, probably, because of its instability in Escherichia coli.

Cloning, Molecular↗
PubMed1984

Chromosomal mapping of murine c-fes and c-src genes.

The murine homologs of two viral oncogenes associated with tyrosine-specific kinase activity have been assigned to different loci in the mouse genome. The segregation of restriction site polymorphisms, as detected by probes that are specific for endogenous c-fes and c-src sequences, was followed in the DNA of recombinant inbred strains. The c-fes gene was mapped to the proximal portion of chromosome 7, very close to the Gpi-1 locus, whereas c-src was linked to the Psp locus on the distal half of chromosome 2.

Alleles↗
PubMed1988

c-src gene product in developing rat brain is enriched in nerve growth cone membranes.

Differentiating rat neurons express high levels of the protooncogene product pp60c-src, a 60-kDa tyrosine kinase of unknown function encoded by c-src. pp60c-src was found to be concentrated at least 9-fold in membranes from a subcellular fraction of nerve growth cones, the motile tips of outgrowing neuronal processes. Indirect immunofluorescence staining of cultured chick retinal explants showed pp60c-src in neuronal growth cones and processes, with the antigen particularly concentrated in growth cones of long neurites. pp60c-src in growth cone membranes was an active tyrosine-specific protein kinase with elevated tyrosine-specific protein kinase activity and reduced electrophoretic mobility characteristic of the form of pp60c-src in central nervous system neurons. pp60c-src was present at lower levels in subcellular fractions from mature rat brain but synaptosomal membranes were not enriched. Preferential localization of an active form of pp60c-src in nerve growth cone membranes and persistence of pp60c-src in mature neurons suggest that this tyrosine kinase is important in growth cone-mediated neurite extension and synaptic plasticity.

Animals↗
PubMed2001

Activation of c-Src gene product in hepatocellular carcinoma is highly correlated with the indices of early stage phenotype.

BACKGROUND/AIMS: The aim of this study was to investigate whether c-Src is involved in carcinogenesis and progression of human hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. METHODS: We designed an immunohistochemical study using Clone 28, an antibody that specifically recognizes the activated form of c-Src. RESULTS: Hepatocytes in normal liver, chronic hepatitis with or without cirrhosis, atypical adenomatous hyperplasia, as well as bile ductular cells, and infiltrating mononuclear cells were all negative for immunohistochemical staining for the activated c-Src. Among 87 cases of HCC tested, 40 (46%) were positively stained for the activated c-Src, and this positive staining was inversely correlated with the Ki-67 labeling index (LI) (P = 0.0031), intrahepatic metastasis (P = 0.0099), TNM stage (P = 0.0062), alpha-fetoprotein (P = 0.0103) and epidermal growth factor-receptor expression (P = 0.0153). Positive staining for the activated c-Src was more frequently observed in well- or moderately-differentiated carcinoma (P = 0.0256). In multivariate analysis, the activated c-Src expression was independently related to the Ki-67 LI (P = 0.0197). In contrast to positive staining in HCC, cholangiocarcinoma were classified as negative in all 19 cases examined. CONCLUSIONS: These results strongly suggest the involvement of activated c-Src in early stages of HCC, and suggest that cholangiocarcinoma might employ different signaling mechanisms.

Carcinoma, Hepatocellular↗
PubMed1982

Expression of the ASV src gene in hybrids between normal and virally transformed cells: specific suppression occurs in some hybrids but not others.

Somatic cell hybrids have been made between clones of rat cells transformed by avian sarcoma virus and rat or mouse cells that are untransformed. Intraspecies hybrids were either predominantly morphologically normal or predominantly transformed, some clones that formed transformed intraspecies hybrids yielding normal interspecies hybrids. Untransformed hybrids usually showed no detectable alteration in the structure or location of the integrated provirus, but viral RNA and pp60src kinase activities were much reduced. No decrease in viral gene expression was seen in transformed hybrids. Thus hybrid suppression of viral transformation, mediated in trans by the untransformed parent, is a specific event that depends on both untransformed and transformed parental parameters.

Animals↗
PubMed1984

Modifications in the phosphorylation of cell proteins related to the expression of src gene in chicken embryo fibroblasts.

The possible physiological targets of pp60src in chicken embryo fibroblasts transformed by Rous sarcoma virus were looked for by a general screening of the modifications of phosphorylation of the major cell phosphoproteins. These modifications were analyzed quantitatively by SDS-PAGE of total cell proteins on gradient gels, combined with a computerized densitometric evaluation of gel autoradiographies, using cells labeled with either [14C]-amino acids or with [32P]-phosphate. A large numbers of proteins, 37 out of the 68 studied, were found to be more phosphorylated in virally transformed cells. The determination of the phosphoamino acid content of proteins which were more phosphorylated in transformed cells and the study of the kinetics of protein phosphorylation in cells infected by a ts mutant, after a shift from the nonpermissive to the permissive temperature, showed that, among these proteins, five displayed a large increase in phosphotyrosine content and an early increase in phosphorylation after the temperature shift. These proteins of 36 K, 41 K, 46 K, 65 K and 280-300 K doublet are therefore good candidates for being physiological targets of pp60src in the cell.

Animals↗
PubMed1987

Amiloride inhibits the protein tyrosine kinases associated with the cellular and the transforming src-gene products.

Amiloride inhibits a protein tyrosine kinase from rat brain extracts. The kinase activity is characterized by an anti-serum (TBR-serum) which immunoprecipitates pp60c-src, the cellular counterpart of the transforming protein pp60v-src of Rous sarcoma virus. In immunocomplexes, TBR-IgG serves as an artificial but specific phosphate acceptor. The phosphate incorporation into TBR-IgG is a time- and temperature-dependent process. In the presence of amiloride the TBR-IgG phosphorylation is reduced. The drug does not influence the immunocomplexes formed by TBR-IgG and pp60src and no amiloride-activated protein tyrosine phosphatase can be detected in the immunocomplex system. Half-maximal inhibition of the tyrosine kinase occurs at 300 microM amiloride and is competitive with respect to ATP. Viral pp60src kinase of transformed cells is more sensitive to amiloride (IC50: 50-100 microM). Furthermore, normal cellular tyrosine kinases are to a lesser extent inhibited by amiloride as compared to the transforming viral pp60src kinase. These results may indicate different amiloride-sensitive forms of cellular pp60src kinases.

Adenosine Triphosphate↗
PubMed1980

Localization of the src gene product of the Harvey strain of MSV to plasma membrane of transformed cells by electron microscopic immunocytochemistry.

Using electron microscopic immunocytochemistry, we have investigated the intracellular location of the src protein (p21) in cells transformed by the Harvey strain of Murine Sarcoma Virus (Ha-MSV). Antibodies to p21 were derived from tumor-bearing rats inoculated with Ha-NRK cells. The distribution of p21 in intracellular sites in MDCK dog cells transformed by Ha-MSV was examined and quantified using a recently developed immunocytochemical technique. More than 95% of p21 was localized to the inner surface of the plasma membrane in these Ha-MSV-transformed cells; p21 was not exposed on the outside surface of the plasma membrane. A similar location was observed by immunofluorescence in other Ha-MSV-transformed cell lines, including cells derived from rat, mouse and mink. This finding, and the previous demonstration that p60src of avian sarcoma virus is concentrated on the inner surface of the plasma membrane, suggests that the plasma membrane is a major site of action for transforming proteins.

Animals↗
PubMed1989

Multiple regions in the Rous sarcoma virus src gene intron act in cis to affect the accumulation of unspliced RNA.

Retrovirus replication requires the production of both spliced and unspliced viral RNA from a single RNA transcript. In contrast, cellular RNA precursors with introns almost completely spliced. The cis elements and virus-coded trans factors which determine the extent to which Rous sarcoma virus RNA is spliced to src mRNA were investigated by transfecting chicken embryo fibroblasts with cloned wild-type and mutant DNA followed by the analysis of viral RNA. Two cis-acting regions important in the negative control of splicing were detected. Cell cultures transfected with a clone deleted in 80% of the src intron (nucleotide 1149 to nucleotide 6574) demonstrated only a 2-fold reduction in the ratio of unspliced to spliced RNA relative to the wild-type clone, whereas cultures transfected with clones which were further deleted in the gag gene region (between nucleotide 630 and nucleotide 5258) demonstrated an approximate 20-fold reduction. Cell cultures which were transfected with clones deleted only between nucleotides 543 and 1806 demonstrated only a three- to fourfold reduction in the unspliced-to-spliced RNA ratio, suggesting that at least one other region of the src intron can partially compensate for the deletion of the gag region. Both regions appeared to act in cis on the distribution of unspliced and spliced RNA since the ratios were not altered by cotransfection with helper virus DNA.

Animals↗
PubMed1987

Analysis of the c-src gene product structure, abundance, and protein kinase activity in human neuroblastoma and glioblastoma cells.

We have compared in different human neuroblastoma cell lines and human glioblastoma cells the expression level, structure, and tyrosine-specific protein kinase activity of pp60c-src. Our results show that not all human neuroblastoma cell lines express pp60c-src molecules with amino-terminal structural alterations. In neuroblastoma cells which possess pp60c-src with altered gel migration, the diminished polyacrylamide gel mobility of pp60c-src was found not to be dependent upon amino-terminal phosphorylations since extensive treatment of these molecules with phosphatase did not significantly change their gel migration properties. Similar differences in gel migration were observed when RNA from the various neuroblastoma and glioblastoma cells was translated in vitro using either rabbit reticulocyte or wheat germ lysates. White the level of c-src mRNA in the different cells analyzed was found to be similar, the abundance of pp60c-src in these same cells was found to vary by as much as 12-fold. This suggests that the abundance of pp60c-src in human neuroendocrine tumors is regulated through post-transcriptional and/or post-translational events which may be related to the stage of neuronal differentiation of the cells. Based upon determination of pp60c-src abundance by immunoblot analysis, we demonstrate that pp60c-src molecules derived from human neuroblastoma and glioblastoma cells have very similar in vitro protein kinase activities.

Antibodies, Monoclonal↗
PubMed1989

A rat mutant cell clone showing temperature-dependent transformed phenotypes with functional expression of the src gene product.

The cellular mutant B814 isolated from a Fischer rat cell line shows temperature-sensitivity of focus formation on infection with Moloney murine sarcoma virus (Mo-MSV) and Rous sarcoma virus (RSV). An RSV-transformed clone (S814-2) isolated from B814 cells shows temperature-sensitive transformed phenotypes for morphology, growth in soft agar, and glucose uptake. The expression, phosphorylation, and tyrosine kinase activity of pp60v-src in S814-2 were not affected at the nonpermissive temperature, and virus rescued from this clone had wild-type transforming ability, suggesting that a cellular factor altered in S814-2 is responsible for the cellular steps of transformation after the function of pp60v-src. In addition, the cellular 36K protein, a possible candidate as a target of pp60v-src, was phosphorylated at the nonpermissive temperature in S814-2, indicating that phosphorylation of the 36K protein is not correlated with transformed phenotypes.

Animals↗