Disease relevance of SRC

• The Rous sarcoma virus oncogene product, pp60v-src, transforms cultured fibroblasts but its corresponding proto-oncogene product, pp60c-src, does not [1].
• Expression of pp60c-src persisted in mature neuronal cells that were postmitotic, fully differentiated, and functional. pp60c-src immunoreactivity was localized within processes and cell bodies of ganglion neurons, processes of rods and cones, and in some but not all neurons of the inner nuclear layer [2].
• Activation of cSrc and expression of the HO-1 gene product are each induced under conditions of hypoxia [3].
• A difference of 25 g was observed between the mean body weights of SDR males and females and between the SDS males and females after one generation of selection [4].
• The SDR males and females had an average of 17% increase in weight gain at 21 days of age when fed the -Se diet compared with the control line males and females fed the same diet for the three generations of selection [4].

High impact information on SRC

• Dynamic coupling between the SH2 and SH3 domains of c-Src and Hck underlies their inactivation by C-terminal tyrosine phosphorylation [5].
• A mutational analysis of c-Src expressed in Schizosaccharomyces pombe demonstrates that replacement of residues in the SH2-SH3 connector with glycine activates c-Src [5].
• Purified maturation promoting factor phosphorylates pp60c-src at the sites phosphorylated during fibroblast mitosis [6].
• These results suggest that pp60c-src is one of the targets for MPF action, which may account in part for the pleiotropic changes in protein phosphorylation and cellular architecture that occur during mitosis [6].
• We have previously shown that overexpressed chicken pp60c-src has retarded mobility, novel serine/threonine phosphorylation, and enhanced kinase activity during NIH 3T3 cell mitosis [6].

Chemical compound and disease context of SRC

• The transforming protein of Rous sarcoma virus (pp60v-src) and its normal cellular homologue (pp60c-src) appear to be protein kinases that phosphorylate tyrosine in a variety of protein substrates [7].

Biological context of SRC

• The c-src gene consists of 12 exons; the boundaries of the exons were determined by assuming that the amino acid sequence of its product, pp60c-src, is basically the same as that of pp60v-src [8].
• The deduced amino acid sequence of pp60c-src was very similar to that of pp60v-src, but the last 19 carboxy-terminal amino acids of pp60c-src were replaced by a new set of 12 amino acids of pp60v-src [8].
• All of these RNAs have the potential of coding for pp60c-src, since their 5' exons are all eventually joined to exon 2 [9].
• An open reading frame of 217 amino acids, called sdr (src downstream region), was found 105 nucleotides from the termination codon for pp60c-src [9].
• We introduced two mutations into the carboxy-terminal regulatory region of chicken pp60c-src [10].

Anatomical context of SRC

• While the c-src locus is expressed as a 4.0-kilobase (kb) mRNA coding for pp60c-src in various chicken tissues, including embryonic muscle, it is expressed as a novel 3.0-kb mRNA in adult skeletal muscle [11].
• Thus the use of a highly specific antibody reveals that enzymatically active pp60v-src and pp60c-src molecules are present in other intracellular structures, probably juxtareticular nuclear membranes, in addition to the plasma membrane in normal, uninfected, and wild-type RSV-infected cells [12].
• Initial studies of pp60c-src in chick lens tissues during development indicate that higher kinase activity is found in the epithelial cells relative to mature lens fibres [13].
• A monoclonal antibody to a 60-kDa substrate of the insulin receptor tyrosine kinase is utilized in the present studies to examine this molecule in 3T3 cells expressing either the transforming chicken c-Src (mutant Phe-527), the wild type molecule, or the parental cells [14].
• In this study, we have used this antibody as an in vitro activator and purified a c-Src-related protein-tyrosine kinase from the particulate fraction of Xenopus laevis oocytes [15].

Associations of SRC with chemical compounds

• In this study, it was observed that the tyrosine phosphorylated in pp60c-src is Tyr527, six residues from the COOH-terminus of the protein [1].
• Activation of YRP kinase by protein kinase C was found to be potentiated by vanadate treatment or overexpression of c-Src [16].
• We have identified two phosphotyrosine-containing cellular proteins with relative molecular masses of 130,000 (pp130) and 110,000 (pp110) daltons in chicken embryo cells that coimmunoprecipitated with pp60v-src and activated forms of chicken pp60c-src (pp60(527)F) [17].
• Nongenomic action of 1 alpha,25(OH)(2)-vitamin D3. Activation of muscle cell PLC gamma through the tyrosine kinase c-Src and PtdIns 3-kinase [18].
• 1 alpha,25(OH)(2)D(3)-induced membrane translocation of PLC gamma was prevented to a great extent by c-Src and PtdIns3K inhibitors, PP1 and LY294002 [18].

Enzymatic interactions of SRC

• The chicken proto-oncoprotein c-Src is phosphorylated by p34cdc2 during mitosis concomitant with increased c-Src tyrosine kinase activity [19].
• We recently identified a novel protein tyrosine kinase that specifically phosphorylates truncated pp60c-src (Mr = 53,000) at a tyrosine residue(s) distinct from its autophosphorylation site [20].

Other interactions of SRC

• Regulatory role for SRC and phosphatidylinositol 3-kinase in initiation of fibronectin matrix assembly [21].
• Since complex formation between c-Src and CSK seemed a likely regulatory step in the control of c-Src kinase activity, such an association was investigated by immunoprecipitation and Western blotting as well as intracellular localization studies [22].
• We demonstrated that c-Src co-immunoprecipitates with gelsolin, and that osteopontin stimulates its activity [23].
• We observed that pp60c-src activity in crypt cytoskeleton was higher (on average, fourfold as measured by enolase phosphorylation or sevenfold as measured by autophosphorylation) than that in cytoskeletons from differentiated enterocytes [24].

Analytical, diagnostic and therapeutic context of SRC

• Molecular cloning and expression of chicken C-terminal Src kinase: lack of stable association with c-Src protein [22].
• Non-neuronal and neuronal forms of intact pp60c-src were separately purified from the membrane fraction of neonatal rat brain by sequential column chromatographies [20].
• Both the nuclear and nucleolar stainings can be totally extinguished by preincubation of the serum with highly purified chicken c-Src [25].
• Phosphotyrosine-modified proteins that were potential targets of pp60c-src increased following nerve crush, and were localized to outgrowing neurites as well as to nonneuronal cells [26].
• The kinase migrated on two-dimensional gel electrophoresis with an apparent pI and molecular mass similar to pp60c-src [27].

References