c-Src, Receptor Tyrosine Kinases, and Human Cancer

Biscardi, Jacqueline S.; Tice, David A.; Parsons, Sarah J.

doi:10.1016/s0065-230x(08)60774-5

Cited by 223 publications

(178 citation statements)

References 360 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…We also observed a basal tyrosine kinase activity in immunoprecipitates of c-Src from hepatocyte lysates, which was inhibited by CGP77675, but so far we have not found any significant increase of this kinase activity after EGF stimulation (data not shown). The data support the notion that although c-Src tyrosine kinase activity is required for EGF-induced Stat5b activation, this might reflect a cooperation between cSrc and the EGF receptor and not necessarily c-Src activation as a direct downstream effect of the EGF receptor (Biscardi et al, 1999;Abram and Courtneidge, 2000;Reddy et al, 2000;Garcia et al, 2001).…”

Section: Discussionsupporting

confidence: 81%

“…Src tyrosine kinase seems to be involved in signaling from certain receptor tyrosine kinases and cytokine receptors and may activate Stat3 in some cell models (Bromberg et al, 1998b;Turkson et al, 1998;Biscardi et al, 1999;Abram and Courtneidge, 2000). Src has also been reported to activate Stat5 (Kazansky et al, 1999;Reddy et al, 2000), and recent findings in A431 and HepG2 cells suggest that c-Src may be involved in EGF receptor-mediated activation of Stat5 (Olayioye et al, 1999;Wang et al, 1999), while PDGF-induced Stat5 activation was independent of c-Src and c-Fyn in some transfected cells and cell-free systems (Paukku et al, 2000).…”

Section: Constitutive Serine Phosphorylation Of Stat5bmentioning

confidence: 99%

See 1 more Smart Citation

EGF receptor‐mediated, c‐Src‐dependent, activation of Stat5b is downregulated in mitogenically responsive hepatocytes

Guren

Ødegård

Abrahamsen

et al. 2003

Journal Cellular Physiology

View full text Add to dashboard Cite

Signal transducer and activator of transcription (STAT) proteins may be activated by epidermal growth factor (EGF), but their role in EGF receptor-mediated mitogenic signaling is not clear. We previously showed that Stat5b was activated by EGF in rat hepatocytes in primary monolayer culture. In the present study, we found that EGF induced tyrosine phosphorylation of Stat5b both on Tyr-699, which correlated with specific DNA binding activity, and also on other tyrosine residues. The Src tyrosine kinase inhibitor CGP77675 blocked the EGF-induced activation of Stat5b, but did not affect the Stat5b activation by growth hormone (GH) or prolactin (PRL). The Stat5b response to EGF was most pronounced soon (3 h) after plating (early G 1 ) and at high cell density (50,000 hepatocytes per cm 2 ). However, at this cell density EGF did not stimulate DNA synthesis. In hepatocytes at 24 h of culturing (mid/late G 1 ) with 20,000 cells per cm 2 , EGF induced strong phosphorylation of the EGF receptor, as well as Shc and ERK, and stimulated DNA synthesis, but did not activate Stat5b, although the Stat5b response to GH or PRL was retained. A strong GHinduced Stat5b activation neither influenced the DNA synthesis alone nor enhanced the mitogenic effect of EGF. The results show that EGF induces tyrosine phosphorylation and DNA-binding activity of Stat5b in a manner different from GH and PRL, apparently by a Src-dependent mechanism. The data also provide further evidence that Stat5b is not required for mitogenic signaling from the EGF receptor.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Constitutive Serine Phosphorylation Of Stat5bmentioning

confidence: 99%

EGF receptor‐mediated, c‐Src‐dependent, activation of Stat5b is downregulated in mitogenically responsive hepatocytes

Guren

Ødegård

Abrahamsen

et al. 2003

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…[10][11][12] SRC also contributes to cancer development. [13][14][15] SRC is activated in various kinds of cancers including breast cancer, colorectal cancer, and melanoma. 16,17 The different levels of SRC activation in primary and metastatic melanomas suggest involvement of SRC in the progression of melanoma, 18 which is consistent with the correlation between increases in SRC kinase activity and the progression of malignancy observed in colon cancer.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis-associated tyrosine kinase 1 inhibits growth and migration and promotes apoptosis in melanoma

Rubin

2014

Laboratory Investigation

View full text Add to dashboard Cite

Apoptosis-associated tyrosine kinase 1 (AATK1) was initially identified as a protein that was dramatically overexpressed during growth arrest and apoptosis of 32Dcl myeloblastic leukemia cells. AATK is expressed in different regions of the brain and may have a role in normal nervous system development by its dual functions of enhancing apoptosis of mature granule cells and promoting terminal neuronal differentiation of developing neurons. However, its function in cancer has never been studied. Melanoma is a tumor composed of transformed cells within the melanocyte lineage deriving from the embryonic neural crest. It has been shown that developmental pathways in neural crest cells have a direct bearing on melanoma formation and human metastatic melanoma cells express a dedifferentiated phenotype. We found that the expression levels of AATK are lower in metastatic melanoma cell lines compared with primary melanoma cell lines and normal human melanocytes. We found that depletion of AATK mRNA in metastatic melanoma cell lines enhanced cell migration in cell line derived from metastatic melanomas. Overexpression of AATK inhibited cell proliferation, colony formation, and promoted apoptosis in melanoma cell lines derived from primary and metastatic melanomas. Signal transduction pathway analysis revealed that Src is involved in regulating AATK. Our results demonstrate for the first time that AATK inhibits cell proliferation, colony formation, and migration, and also promotes apoptosis in melanoma cells.

show abstract

“…In some cases, the genes that are activated during these processes have been identified and they include, cyclin D1, c-myc, bcl xL , and p53. The c-Src tyrosine kinase is also overexpressed in a number of solid tumors including colon, breast, SCCHN, pancreatic, and lung among others (Biscardi et al, 1999b). Models of breast cancer and squamous cell carcinoma of the head and neck (SCCHN) have provided mechanistic insight into the role of STAT proteins in c-Src overexpressing tumors.…”

Section: Introductionmentioning

confidence: 99%

Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis

2004

View full text Add to dashboard Cite

c-Src, Receptor Tyrosine Kinases, and Human Cancer

Cited by 223 publications

References 360 publications

EGF receptor‐mediated, c‐Src‐dependent, activation of Stat5b is downregulated in mitogenically responsive hepatocytes

EGF receptor‐mediated, c‐Src‐dependent, activation of Stat5b is downregulated in mitogenically responsive hepatocytes

Apoptosis-associated tyrosine kinase 1 inhibits growth and migration and promotes apoptosis in melanoma

Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis

Contact Info

Product

Resources

About