Purification of a 72-kDa Protein-Tyrosine Kinase from Rat Liver and Its Identification as Syk: Involvement of Syk in Signaling Events of Hepatocytes

Tsuchida, Shinobu; Yanagi, Shigeru; Inatome, Ryoko; Ding, Junyi; Hermann, Patrice; Tsujimura, Takuya; Matsui, Noriko; Yamamura, Hirohei

doi:10.1093/oxfordjournals.jbchem.a022610

Cited by 41 publications

(44 citation statements)

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“…So, it has been suggested that nonhemopoietic cells do not exhibit Syk expression. As this manuscript was being completed, Wang et al (30), using a strategy of reverse transcription and PCR, reported that 3T3-L1 mouse embryonic fibroblasts expressed Syk, and Tsuchida et al (31) reported that hepatocytes expressed Syk. We also found Syk expression in human nasal polyp-derived fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Protein-Tyrosine Kinase Syk Expressed in Human Nasal Fibroblasts and Its Effect on RANTES Production

Yamada

Fujieda

Yanagi

et al. 2001

The Journal of Immunology

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Fibroblasts, a rich source of chemokines, interact with eosinophils and play a key role in the pathogenesis of airway disease. RANTES is produced by fibroblasts to attract and activate eosinophils. LPS is known to induce RANTES and cause protein tyrosine phosphorylation. Nonreceptor protein tyrosine kinase Syk is widely expressed and an important role in intracellular signal transduction in hemopoietic cells. In the present study, we examined whether Syk was expressed in a number of primary human nasal polyp tissue-derived fibroblast lines and whether it played some role in cellular function. Syk proteins were expressed in human nasal fibroblasts, but the expression level varied. There were positive correlations between the level of Syk expression and RANTES production induced by LPS. Overexpression of wild-type Syk by gene transfer enhanced RANTES production from nasal fibroblasts stimulated with LPS. The decrease of Syk expression by the administration of Syk antisense inhibited RANTES production. These results suggest that Syk expression affects RANTES production in fibroblasts of nasal polyps.

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Section: Discussionmentioning

confidence: 99%

Protein-Tyrosine Kinase Syk Expressed in Human Nasal Fibroblasts and Its Effect on RANTES Production

Yamada

Fujieda

Yanagi

et al. 2001

The Journal of Immunology

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“…Phosphorylation of phospholipase C␥2 by Syk results in downstream activation of p44/p42 MAPK and JNK kinases (28), whereas PI3K phosphorylation by Syk mediates Akt activity (29). Recent evidence indicates that Syk is also expressed in nonhemopoietic cells, including hepatocytes (30), colon cancer cells (31), and breast cancer cells (32).…”

Section: Tnf Activates Syk Proteinmentioning

confidence: 99%

TNF Activates Syk Protein Tyrosine Kinase Leading to TNF-Induced MAPK Activation, NF-κB Activation, and Apoptosis

Takada

Aggarwal

2004

The Journal of Immunology

108

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Spleen tyrosine kinase (Syk), a nonreceptor protein kinase initially found to be expressed only in hemopoietic cells, has now been shown to be expressed in nonhemopoietic cells and to mediate signaling of various cytokines. Whether Syk plays any role in TNF signaling was investigated. Treatment of Jurkat T cells with TNF activated Syk kinase but not ZAP70, another member of Syk kinase family, and the optimum activation occurred at 10 s and with 1 nM TNF. TNF also activated Syk in myeloid and epithelial cells. TNF-induced Syk activation was abolished by piceatannol (Syk-selective inhibitor), which led to the suppression of TNF-induced activation of c- JNK, p38 MAPK, and p44/p42 MAPK. Jurkat cells that did not express Syk (JCaM1, JCaM1/lck) showed lack of TNF-induced Syk, JNK, p38 MAPK, and p44/p42 MAPK activation, as well as TNF-induced IκBα phosphorylation, IκBα degradation, and NF-κB activation. TNF-induced NF-κB activation was enhanced by overexpression of Syk by Syk-cDNA and suppressed when Syk expression was down-regulated by expression of Syk-small interfering RNA (siRNA-Syk). The apoptotic effects of TNF were reduced by up-regulation of NF-κB by Syk-cDNA, and enhanced by down-regulation of NF-κB by siRNA-Syk. Immunoprecipitation of cells with Syk Abs showed TNF-dependent association of Syk with both TNFR1 and TNFR2; this association was enhanced by up-regulation of Syk expression with Syk-cDNA and suppressed by down-regulation of Syk using siRNA-Syk. Overall, our results demonstrate that Syk activation plays an essential role in TNF-induced activation of JNK, p38 MAPK, p44/p42 MAPK, NF-κB, and apoptosis.

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“…Although cancer-associated CpG island hypermethylation tends to occur in inactive genes in normal cells, 21 SYK methylation develops despite its active expression in normal hepatocytes. 22 Considering that previous studies and the present study have indicated that SYK promoter CpG island hypermethylation is closely associated with poorer prognosis in HCC patients, 10,23 it could be hypothesized that the reduced expression of SYK by promoter CpG island hypermethylation may be related to the biological aggressiveness of HCC.…”

Section: Discussionmentioning

confidence: 69%

Downregulation of spleen tyrosine kinase in hepatocellular carcinoma by promoter CpG island hypermethylation and its potential role in carcinogenesis

Shin

Kim

Lee

et al. 2014

Laboratory Investigation

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Spleen tyrosine kinase (SYK) has predominantly been studied in hematopoietic cells, where it is involved in immunoreceptor-mediated signaling. However, SYK expression has been shown in numerous non-hematopoietic cells, and its downregulation has been shown to be involved in tumor formation and progression. SYK methylation has been demonstrated to identify a subset of hepatocellular carcinoma (HCC) cases with poor prognosis, but little is known regarding the biological role of SYK in HCC. We found that SYK methylation is a common event in HCC, and is inversely associated with its expression. We established stable HCC cell lines with inducible SYK expression vectors, and compared the differential RNA expression profiles of HCC cell lines with or without the induction of SYK. Gene ontology analysis revealed that the SYK-regulated genes were enriched for genes involved in cell adhesion. Accordingly, we found that the induction of SYK expression increased the adhesion of cells to fibronectin and decreased cell migration and invasion, and that cessation of SYK overexpression increased cell migration and invasion. Our findings suggest that SYK is involved in regulating cell to matrix adhesions, and that SYK loss affects the migration, and invasion of HCC cells. (2014) 94, 1396-1405 doi:10.1038/labinvest.2014 published online 13 October 2014 Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. In men, it ranks the fifth most common cancer worldwide and is the second leading cause of cancer death, with an estimate of 4520 000 new cases each year. 1 The major risk factors associated with the incidence of HCC are well established, and include infection by hepatitis B and hepatitis C viruses, chronic alcoholism, and aflatoxin exposure. 2 However, the molecular carcinogenesis pathways involving the development and progression of HCC remain largely unclear. Like most solid tumors, it has been believed that the progression of HCC occurs as a consequence of a series of genetic and epigenetic alterations. 2 Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that is widely expressed in hematopoietic cells. Recently, SYK expression has been demonstrated in numerous nonhematopoietic cells, and its downregulation has been shown to be involved in tumor formation and progression. [3][4][5][6] The transfection of SYK into an SYK-negative cancer cell line dramatically inhibited its cell growth, migration, and invasion. [3][4][5][6] Conversely, the knockdown of SYK in SYK-positive breast cancer cells increased proliferation and invasion. 7 Several researchers have also reported that the loss of SYK expression correlates with poor survival and tumor metastasis in patients with breast, 8 bladder, 9 liver, 10 pancreas, 5 or stomach cancer. 11 Epigenetic silencing through hypermethylation of promoter CpG islands has been proposed to be involved in the loss of SYK expression in these tumors. [3][4][5][6] Although SYK was shown to affect cell proliferation, motility, and invasion in several types of c...

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Purification of a 72-kDa Protein-Tyrosine Kinase from Rat Liver and Its Identification as Syk: Involvement of Syk in Signaling Events of Hepatocytes

Cited by 41 publications

References 0 publications

Protein-Tyrosine Kinase Syk Expressed in Human Nasal Fibroblasts and Its Effect on RANTES Production

Protein-Tyrosine Kinase Syk Expressed in Human Nasal Fibroblasts and Its Effect on RANTES Production

TNF Activates Syk Protein Tyrosine Kinase Leading to TNF-Induced MAPK Activation, NF-κB Activation, and Apoptosis

Downregulation of spleen tyrosine kinase in hepatocellular carcinoma by promoter CpG island hypermethylation and its potential role in carcinogenesis

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