Transformation of Rat-1 fibroblasts with the v-src oncogene leads to a 6- to 8-fold enhancement of the activity of the Ins(1,4,5)P3 3-kinase in cytosolic extracts [Johnson, Wasilenko, Mattingly, Weber and Garrison (1989) Science 246, 121-124]. This study confirms these results using another v-src-transformed Rat-1 cell line (B31 cells) and investigates the molecular mechanism by which pp60v-src activates Ins(1,4,5)P3 3-kinase. The mRNA and protein levels for two rat isoforms of Ins(1,4,5)P3 3-kinase were determined in the v-src-transformed cell line. Both the mRNA and protein levels for isoform A were elevated in v-src-transformed Rat-1 cells while those for isoform B were not significantly affected. Moreover, stable expression of either form of Ins(1,4,5)P3 3-kinase in the B31 v-src-transformed Rat-1 cell line did not result in tyrosine phosphorylation of Ins(1,4,5)P3 3-kinase A or B. These results suggest that at least one mechanism by which the v-src oncogene increases the activity of the ...

TY - JOUR. T1 - Radicicol, an Agent Inducing the Reversal of Transformed Phenotypes of src-Transformed Fibroblasts. AU - Kwon, Ho Jeong. AU - Yoshida, Minoru. AU - Abe, Keiichi. AU - Horinouchi, Sueharu. AU - Beppu, Teruhiko. PY - 1992/1/1. Y1 - 1992/1/1. UR - http://www.scopus.com/inward/record.url?scp=0026823291&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0026823291&partnerID=8YFLogxK. U2 - 10.1271/bbb.56.538. DO - 10.1271/bbb.56.538. M3 - Article. C2 - 1368339. AN - SCOPUS:0026823291. VL - 56. SP - 538. EP - 539. JO - Bioscience, Biotechnology and Biochemistry. JF - Bioscience, Biotechnology and Biochemistry. SN - 0916-8451. IS - 3. ER - ...

Podosomes mediate cell migration and invasion by coordinating the reorganization of actin cytoskeleton and focal matrix degradation. MMP and serine proteases have been found to function at podosomes. The lysosomal cysteine cathepsins, a third major class of matrix-degrading enzymes involved in tumor invasion and tissue remodeling, have yet to be linked to podosomes with the exception of cathepsin K in osteoclasts. Using inhibitors and shRNA-mediated depletion, we show that cathepsin B participates in podosomes-mediated focal matrix degradation and invasion in v-Src-transformed fibroblasts. We observed that lysosomal marker LAMP-1 localized at the center of podosome rosettes protruding into extracellular matrix using confocal microscopy. Time-lapse live-cell imaging revealed that lysosomal vesicles moved to and fused with podosomes. Disruption of lysosomal pH gradient with Bafilomycin A1, chloroquine, or ammonium chloride greatly enhanced the formation of podosomes and increased the matrix degradation.

It seemed that the state of tyrosine phosphorylation was not altered by the expression of the caveolin-1 mutant. We next used a variety of phospho-specific antibodies (12) that have been generated against the activated forms of well-known signal transducers. Fig. 4d ⇓ shows that both intracellular MAPKs and p38-MAPK 4 were constitutively activated in the caveolin-1 mutant clones. On the other hand, the status of phosphorylation of AKT was not changed, although v-Src-transformed cells (SR3Y1) showed increased phosphorylation of AKT. Again, these experiments demonstrated the capacity for the mutant to drive cell transformation. These observations are compatible with previous reports showing that alteration of caveolin-1 function could be involved in the cellular transformation as a dominant negative effect of caveolin-1.. The mutation-positive cases of breast cancer were mostly involved in the pathologically invasive types such as scirrhous carcinomas (18) . Hence, we suspected that the ...

A tyrosine-specific protein kinase encoded by the v-src oncogene of ROUS SARCOMA VIRUS. The transforming activity of pp60(v-src) depends on both the lack of a critical carboxy-terminal tyrosine phosphorylation site at position 527, and the attachment of pp60(v-src) to the plasma membrane which is accomplished by myristylation of its N-terminal glycine ...

The SRC gene is similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and…

The intracellular protein tyrosine kinase FAK (focal adhesion kinase) was originally identified gy its high level of tyrosine phosphorylation in v-src-transformed cells. FAK is also highly phosphorylated during early development. In cultured cells it is localized to focal adhesion contacts and becom …

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Invasive carcinoma cells use specialized actin polymerization-driven protrusions called invadopodia to degrade and possibly invade through the extracellular matrix (ECM) during metastasis. Phosphorylation of the invadopodium protein cortactin is a master switch that activates invadopodium maturation and function. Cortactin was originally identified as a hyperphosphorylated protein in v-Src-transformed cells, but the kinase or kinases that are directly responsible for cortactin phosphorylation in invadopodia remain unknown. In this study, we provide evidence that the Abl-related nonreceptor tyrosine kinase Arg mediates epidermal growth factor (EGF)-induced cortactin phosphorylation, triggering actin polymerization in invadopodia, ECM degradation, and matrix proteolysis-dependent tumor cell invasion. Both Src and Arg localize to invadopodia and are required for EGF-induced actin polymerization. Notably, Arg overexpression in Src knockdown cells can partially rescue actin polymerization in ...

Matrix-activated integrins can form different adhesion structures. We report that nontransformed fibroblasts develop podosome-like adhesions when spread on fluid Arg-Gly-Asp peptide (RGD)-lipid surfaces, whereas they habitually form focal adhesions on rigid RGD glass surfaces. Similar to classic macrophage podosomes, the podosome-like adhesions are protrusive and characterized by doughnut-shaped RGD rings that surround characteristic core components including F-actin, N-WASP, and Arp2/Arp3. Furthermore, there are 18 podosome markers in these adhesions, though they lack matrix metalloproteinases that characterize invadopodia and podosomes of Src-transformed cells. When nontransformed cells develop force on integrin-RGD clusters by pulling RGD lipids to prefabricated rigid barriers (metal lines spaced by 1-2 μm), these podosomes fail to form and instead form focal adhesions. The formation of podosomes on fluid surfaces is mediated by local activation of phosphoinositide 3-kinase (PI3K) and the ...

c-Src is involved in HGF-mediated OPN production in osteoblasts.Cells were pretreated for 30 min with PP2 or transfected with c-Src mutant and siRNA followed by

TY - JOUR. T1 - Myristylation and amino-terminal phosphorylation are required for activation of pp60(c-src) during mitosis. AU - Kaech, S.. AU - Schnierle, B.. AU - Wyss, A.. AU - Ballmer-Hofer, K.. PY - 1993/1/1. Y1 - 1993/1/1. N2 - pp60(c-src), a cellular tyrosine kinase homologous to the retroviral v-src oncogene, becomes transiently activated during mitosis. Activation is accompanied by phosphorylation of three sites in the amino-terminal regulatory domain of the protein, threonine 34, threonine 46 and serine 72. These sites can be phosphorylated in vitro by a cell cycle-regulated kinase, p34(cdc2), yet this does not result in increased kinase activity of pp60(c-src). pp60(c-src) is negatively regulated by phosphorylation at tyrosine 527, and it has been shown that this site is transiently dephosphorylated in mitotic cells. The importance of tyrosine 527 in the regulation of pp60(c-src) is also emphasized by the fact that oncogenic mutants of pp60(src) lacking tyrosine 527 are constitutively ...

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008 ...

CSK antibody [CSK-04] (c-src tyrosine kinase) for ICC/IF, IP, WB. Anti-CSK mAb (GTX14996) is tested in Human, Mouse samples. 100% Ab-Assurance.