Syk protein‐tyrosine kinase is involved in neuron‐like differentiation of embryonal carcinoma P19 cells

Tsujimura, Takuya; Yanagi, Shigeru; Inatome, Ryoko; Takano, Tomoko; Ishihara, Itsuko; Mitsui, Norihiro; Takahashi, Shun; Yamamura, Hirohei

doi:10.1016/s0014-5793(01)02097-x

Cited by 38 publications

(27 citation statements)

References 24 publications

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“…In agreement with this, we found that CD3 recruitment by a CD3 antibody induced an elevation of [Ca 2ϩ ] i in cultured neurons. The expression of ZAP-70 -related tyrosine kinase in developing neurons (Ishijima et al, 1995;Yoneya et al, 1998), and the reported role of Syk in neurite outgrowth (Tsujimura et al, 2001;Gallagher et al, 2007) is compatible with the notion that Syk/ZAP-70 could be a relevant component of the intracellular transduction pathway connecting CD3 activation and Ca 2ϩ mobilization to negatively control dendritic shaping.…”

Section: Potential Mechanisms For Cd3 Neuronal Functionsupporting

confidence: 78%

The Signaling Adaptor Protein CD3ζ Is a Negative Regulator of Dendrite Development in Young Neurons

Baudouin

Angibaud

Loussouarn

et al. 2008

MBoC

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A novel idea is emerging that a large molecular repertoire is common to the nervous and immune systems, which might reflect the existence of novel neuronal functions for immune molecules in the brain. Here, we show that the transmembrane adaptor signaling protein CD3, first described in the immune system, has a previously uncharacterized role in regulating neuronal development. Biochemical and immunohistochemical analyses of the rat brain and cultured neurons showed that CD3 is mainly expressed in neurons. Distribution of CD3 in developing cultured hippocampal neurons, as determined by immunofluorescence, indicates that CD3 is preferentially associated with the somatodendritic compartment as soon as the dendrites initiate their differentiation. At this stage, CD3 was selectively concentrated at dendritic filopodia and growth cones, actin-rich structures involved in neurite growth and patterning. siRNA-mediated knockdown of CD3 in cultured neurons or overexpression of a loss-of-function CD3 mutant lacking the tyrosine phosphorylation sites in the immunoreceptor tyrosine-based activation motifs (ITAMs) increased dendritic arborization. Conversely, activation of endogenous CD3 by a CD3 antibody reduced the size of the dendritic arbor. Altogether, our findings reveal a novel role for CD3 in the nervous system, suggesting its contribution to dendrite development through ITAM-based mechanisms.

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Section: Potential Mechanisms For Cd3 Neuronal Functionsupporting

confidence: 78%

The Signaling Adaptor Protein CD3ζ Is a Negative Regulator of Dendrite Development in Young Neurons

Baudouin

Angibaud

Loussouarn

et al. 2008

MBoC

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“…Syk is also widely expressed in nonhematopoietic cells like fibroblasts, breast cancer cells, colonic carcinoma cells, hepatocytes, neuronal cells, and vascular endothelial cells (Okamura et al, 1999;Coopman et al, 2000;Tsuchida et al, 2000;Tsujimura et al, 2001;Yamada et al, 2001;Yanagi et al, 2001). Originally, Syk was thought to function primarily in signaling of immunoreceptors such as Fc receptor (FcR) and B cell receptor (BCR).…”

mentioning

confidence: 99%

A Novel Spleen Tyrosine Kinase Inhibitor Blocks c-Jun N-Terminal Kinase-Mediated Gene Expression in Synoviocytes

Cha

Boyle²,

Inoue³

et al. 2006

J Pharmacol Exp Ther

136

118

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“…U -M, methylated; U, unmethylated; Positive expression is marked by "+"; Reduced or lack of expression is designated by "-" cogene is a mechanism for the gene silencing. Syk is expressed in mammary epithelial cells [1], airway epithelial cells [23], human nasal fibroblasts [24], vascular endothelial cells [25], neuron-like cells [26], hepatocytes [27] and melanocytes [28]. The recent identification of Syk as a potent modulator of tumor epithelial cell growth has generated a need for further exploration of the role of nonreceptor tyrosine kinases in wide cancer progression and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Research on the reactivation of Syk expression caused by the inhibition of DNA promoter methylation in the lung cancer

Sw¹,

Ma²,

Xu³

et al. 2011

neo

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The aim of this study was to study the expression of Syk gene and methylation in its promoter region in the lung cancer and to investigate the relationship between silencing of the Syk gene and DNA methylation of the Syk promoter region in lung cancer cell lines.Real-time PCR and immunohistochemistry were used to examine the Syk expression in specimens from 3 lung cancer cell lines and 16 lung cancer patients (tumor tissues and adjacent normal tissues). MSP was used to analyze the methylation status of the Syk promoter region. We also investigated the role of restoring Syk expression by using a DNA methyltransferase inhibitor, 5-aza-CdR, in suppressing invasion of lung cancer cell lines.No expression of the Syk gene was detected in the 3 lung cancer cell lines. In the 16 lung cancer patient samples, Syk expression was significantly lower in the tumor tissues than that in their adjacent normal tissues (P<0.05). Consistently, immunohistochemistry analysis of Syk protein expression showed that in the lung cancer tissues Syk protein expression was also significantly lower than that in their adjacent normal tissues. In the two lung cancer cell lines (NL9980, YTMLC-9) that lack the endogenous Syk expression, 4uM demethylation agent 5-aza-CdR treatment was able to reactivate the Syk gene expression, but not NCI-H446.In conclusion, hypermethylation leads to silencing of the Syk gene in human lung carcinoma cell lines. Methylation of the Syk promoter and loss of Syk expression in lung cancer cell lines are independent biomarkers. Syk may be a potential tumor suppressor in human lung cancer.

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Syk protein‐tyrosine kinase is involved in neuron‐like differentiation of embryonal carcinoma P19 cells

Cited by 38 publications

References 24 publications

The Signaling Adaptor Protein CD3ζ Is a Negative Regulator of Dendrite Development in Young Neurons

The Signaling Adaptor Protein CD3ζ Is a Negative Regulator of Dendrite Development in Young Neurons

A Novel Spleen Tyrosine Kinase Inhibitor Blocks c-Jun N-Terminal Kinase-Mediated Gene Expression in Synoviocytes

Research on the reactivation of Syk expression caused by the inhibition of DNA promoter methylation in the lung cancer

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