keyword
https://read.qxmd.com/read/22683124/the-adaptor-sap-controls-nk-cell-activation-by-regulating-the-enzymes-vav-1-and-ship-1-and-by-enhancing-conjugates-with-target-cells
#21
JOURNAL ARTICLE
Zhongjun Dong, Dominique Davidson, Luis Alberto Pérez-Quintero, Tomohiro Kurosaki, Wojciech Swat, André Veillette
The adaptor SAP, mutated in X-linked lymphoproliferative disease, has critical roles in multiple immune cell types. Among these, SAP is essential for the ability of natural killer (NK) cells to eliminate abnormal hematopoietic cells. Herein, we elucidated the molecular and cellular bases of this activity. SAP enhanced NK cell responsiveness by a dual molecular mechanism. It coupled SLAM family receptors to the kinase Fyn, which triggered the exchange factor Vav-1 and augmented NK cell activation. SAP also prevented the inhibitory function of SLAM family receptors...
June 29, 2012: Immunity
https://read.qxmd.com/read/21871071/efs-shows-biallelic-methylation-in-uveal-melanoma-with-poor-prognosis-as-well-as-tissue-specific-methylation
#22
JOURNAL ARTICLE
Lisa C Neumann, Andreas Weinhäusel, Stefanie Thomas, Bernhard Horsthemke, Dietmar R Lohmann, Michael Zeschnigk
BACKGROUND: Uveal melanoma (UM) is a rare eye tumor. There are two classes of UM, which can be discriminated by the chromosome 3 status or global mRNA expression profile. Metastatic progression is predominantly originated from class II tumors or from tumors showing loss of an entire chromosome 3 (monosomy 3). We performed detailed EFS (embryonal Fyn-associated substrate) methylation analyses in UM, cultured uveal melanocytes and normal tissues, to explore the role of the differentially methylated EFS promoter region CpG island in tumor classification and metastatic progression...
August 26, 2011: BMC Cancer
https://read.qxmd.com/read/21810170/trivanillic-polyphenols-with-anticancer-cytostatic-effects-through-the-targeting-of-multiple-kinases-and-intracellular-ca2-release
#23
JOURNAL ARTICLE
Delphine Lamoral-Theys, Nathalie Wauthoz, Petra Heffeter, Véronique Mathieu, Utte Jungwirth, Florence Lefranc, Jean Nève, Jacques Dubois, François Dufrasne, Karim Amighi, Walter Berger, Philippe Gailly, Robert Kiss
Cancer cells exhibit de-regulation of multiple cellular signalling pathways and treatments of various types of cancers with polyphenols are promising. We recently reported the synthesis of a series of 33 novel divanillic and trivanillic polyphenols that displayed anticancer activity, at least in vitro, through inhibiting various kinases. This study revealed that minor chemical modifications of a trivanillate scaffold could convert cytotoxic compounds into cytostatic ones. Compound 13c, a tri-chloro derivative of trivanillic ester, displayed marked inhibitory activities against FGF-, VEGF-, EGF- and Src-related kinases, all of which are implicated not only in angiogenesis but also in the biological aggressiveness of various cancer types...
July 2012: Journal of Cellular and Molecular Medicine
https://read.qxmd.com/read/21670084/inhibition-of-src-family-kinases-and-receptor-tyrosine-kinases-by-dasatinib-possible-combinations-in-solid-tumors
#24
REVIEW
Juan Carlos Montero, Samuel Seoane, Alberto Ocaña, Atanasio Pandiella
Dasatinib is a small molecule tyrosine kinase inhibitor that targets a wide variety of tyrosine kinases implicated in the pathophysiology of several neoplasias. Among the most sensitive dasatinib targets are ABL, the SRC family kinases (SRC, LCK, HCK, FYN, YES, FGR, BLK, LYN, and FRK), and the receptor tyrosine kinases c-KIT, platelet-derived growth factor receptor (PDGFR) α and β, discoidin domain receptor 1 (DDR1), c-FMS, and ephrin receptors. Dasatinib inhibits cell duplication, migration, and invasion, and it triggers apoptosis of tumoral cells...
September 1, 2011: Clinical Cancer Research
https://read.qxmd.com/read/21523734/a-phase-2-trial-of-dasatinib-in-advanced-melanoma
#25
JOURNAL ARTICLE
Harriet M Kluger, Arkadiuz Z Dudek, Carrie McCann, Jean Ritacco, Nadine Southard, Lucia B Jilaveanu, Annette Molinaro, Mario Sznol
BACKGROUND: Inhibiting src kinases (non-receptor tyrosine kinase signaling intermediates) reduces melanoma cell proliferation and invasion. Dasatinib inhibits c-kit, PDGFβR, and EPHA2 and src kinases c-src, c-Yes, Lck, and Fyn. A phase 2 trial of dasatinib in melanoma was conducted to assess response rate (RR), progression-free survival (PFS), and toxicity. METHODS: Adults with stage 3/4 chemotherapy-naïve unresectable melanoma were eligible. Dasatinib was initially administered at 100 mg twice daily continuously to 17 patients...
May 15, 2011: Cancer
https://read.qxmd.com/read/21480388/fyn-is-induced-by-ras-pi3k-akt-signaling-and-is-required-for-enhanced-invasion-migration
#26
JOURNAL ARTICLE
Vipin Yadav, Mitchell F Denning
Src family kinases (SFKs) are frequently over-expressed and/or activated in human cancers, and play key roles in cancer cell invasion, metastasis, proliferation, survival, and angiogenesis. Allosteric activation of SFKs occurs through well-defined post-translational mechanisms, however the SFK member Fyn is over-expressed in multiple human cancers (prostate, melanoma, pancreatic, glioma, chronic myelogenous leukemia) and the mechanism of increased Fyn expression is unclear. Since activation of Ras oncogenes is a common oncogenic event leading to the activation of multiple effector pathways, we explored if Ras could induce Fyn expression...
May 2011: Molecular Carcinogenesis
https://read.qxmd.com/read/21454696/functional-activation-of-src-family-kinase-yes-protein-is-essential-for-the-enhanced-malignant-properties-of-human-melanoma-cells-expressing-ganglioside-gd3
#27
JOURNAL ARTICLE
Kazunori Hamamura, Momoko Tsuji, Hiroshi Hotta, Yuki Ohkawa, Masataka Takahashi, Hidenobu Shibuya, Hideyuki Nakashima, Yoshio Yamauchi, Noboru Hashimoto, Hisashi Hattori, Minoru Ueda, Keiko Furukawa, Koichi Furukawa
The possible roles of Src family kinases in the enhanced malignant properties of melanomas related to GD3 expression were analyzed. Among Src family kinases only Yes, not Fyn or Src, was functionally involved in the increased cell proliferation and invasion of GD3-expressing transfectant cells (GD3+). Yes was located upstream of p130Cas and paxillin and at an equivalent level to focal adhesion kinase. Yes underwent autophosphorylation even before serum treatment and showed stronger kinase activity in GD3+ cells than in GD3- cells following serum treatment...
May 27, 2011: Journal of Biological Chemistry
https://read.qxmd.com/read/19652529/raking-in-akt-a-tumor-suppressor-function-for-the-intracellular-tyrosine-kinase-frk
#28
REVIEW
Patrick M Brauer, Angela L Tyner
The Fyn related kinase FRK, originally called RAK, is a member of a small family of intracellular Src-related tyrosine kinases that includes PTK6 and Srms. These kinases share a conserved gene structure that is distinct from that of the Src family. Expression of FRK and PTK6 was originally identified in melanoma, breast cancer cells and normal intestinal epithelium, and both FRK and PTK6 have been implicated in the regulation of epithelial cell differentiation and apoptosis. Recently FRK was reported to phosphorylate the tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10), a negative regulator of phosphatidylinositol 3 kinase (PI3K) signaling and AKT activation...
September 1, 2009: Cell Cycle
https://read.qxmd.com/read/18930841/interaction-of-xiphophorus-and-murine-fyn-with-focal-adhesion-kinase
#29
JOURNAL ARTICLE
Janka Teutschbein, Manfred Schartl, Svenja Meierjohann
The Src family kinase/Focal Adhesion Kinase (FAK) complex is a signaling platform playing a crucial role in transformation downstream of oncogenic growth factor receptors. In the case of melanoma in Xiphophorus fish, the oncogenic EGF receptor orthologue Xiphophorus melanoma receptor kinase (Xmrk) effects continuous activation of the Src family kinase Fyn, but not of the other family members Src or Yes. Here, Fyn is strongly involved in promoting many tumorigenic events. Although Fyn is expressed in most mammalian tissues, there are only few reports of its involvement in the development of solid tumors...
March 2009: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://read.qxmd.com/read/16540665/the-oncogenic-epidermal-growth-factor-receptor-variant-xiphophorus-melanoma-receptor-kinase-induces-motility-in-melanocytes-by-modulation-of-focal-adhesions
#30
JOURNAL ARTICLE
Svenja Meierjohann, Elisabeth Wende, Anita Kraiss, Claudia Wellbrock, Manfred Schartl
One of the most prominent features of malignant melanoma is the fast generation of metastasizing cells, resulting in the poor prognosis of patients with this tumor type. For this process, cells must gain the ability to migrate. The oncogenic receptor Xmrk (Xiphophorus melanoma receptor kinase) from the Xiphophorus melanoma system is a mutationally activated version of the epidermal growth factor receptor that induces the malignant transformation of pigment cells. Here, we show that the activation of Xmrk leads to a clear increase of pigment cell motility in a fyn-dependent manner...
March 15, 2006: Cancer Research
https://read.qxmd.com/read/14734741/characterization-of-defective-cd4-cd8-t-cells-in-murine-tumors-generated-independent-of-antigen-specificity
#31
JOURNAL ARTICLE
Robert M Prins, Francesca Incardona, Regan Lau, Paul Lee, Sarah Claus, Wenxuan Zhang, Keith L Black, Christopher J Wheeler
Immune-based therapy confers limited benefits to hosts bearing late-stage tumors. Mounting evidence points to local suppression of T cell function as the most substantial barrier to effective antitumor immunity in hosts with large tumor burdens. Despite this, events responsible for locally defective T cells and immune suppression in tumors remain unclear. We describe in this study a predominant T cell population localized within two murine tumors that is characterized by expression of apoptotic markers and TCRalphabeta/CD3, but not CD4, CD8, or NK-associated markers...
February 1, 2004: Journal of Immunology
https://read.qxmd.com/read/13129922/cooperative-roles-of-fyn-and-cortactin-in-cell-migration-of-metastatic-murine-melanoma
#32
JOURNAL ARTICLE
Jinhong Huang, Tamae Asawa, Tsuyoshi Takato, Ryuichi Sakai
Src family kinases are major regulators of various integrin-mediated biological processes, although their functional roles and substrates in cancer metastasis are unknown. We explored the roles of Src family tyrosine kinases in cell migration and the spread of K-1735 murine melanoma cell lines with low or high metastatic potential. Corresponding to elevated cell motility and spreading ability, Fyn was selectively activated among Src family kinases, and the cell motility was blocked by an inhibitor of Src family kinases...
November 28, 2003: Journal of Biological Chemistry
https://read.qxmd.com/read/12242702/melanoma-development-and-pigment-cell-transformation-in-xiphophorus
#33
REVIEW
Claudia Wellbrock, Ana Gómez, Manfred Schartl
As early as 1927, it was recognised that hybridisation of platyfish (Xiphophorus maculatus) and swordtails (Xiphophorus helleri) results in offspring that develop tumours according to Mendelian laws. Most obviously, the primary event, namely the cell lineage-specific overexpression of a structurally altered receptor tyrosine kinase, finds its parallel in many tumours of birds and mammals. Once expressed at high levels, this receptor, the Xiphophorus melanoma inducing receptor kinase Xmrk, shows constitutive activation...
September 15, 2002: Microscopy Research and Technique
https://read.qxmd.com/read/11858939/interleukin-7-receptor-expression-and-activation-in-nonhaematopoietic-neoplastic-cell-lines
#34
JOURNAL ARTICLE
Larry Cosenza, Gullu Gorgun, Alexander Urbano, Francine Foss
The high-affinity human interleukin-7 (IL-7)R is a heterodimeric complex consisting of the IL-7Ralpha and common interleukin-2 receptor gamma (IL-2Rgamma(c)) chains. Activation of the IL-7R complex is associated with tyrosine and serine residue phosphorylation of a number of intracellular substrates leading to proliferation and induction of various cellular differentiation processes. In this study, we demonstrate, by S1 nuclease protection assay, immunoprecipitation and in vitro kinase assay that functional human (h) IL-7R is expressed in haematopoietic and nonhaematopoietic cell lines...
April 2002: Cellular Signalling
https://read.qxmd.com/read/11734563/activation-of-p59-fyn-leads-to-melanocyte-dedifferentiation-by-influencing-mkp-1-regulated-mitogen-activated-protein-kinase-signaling
#35
JOURNAL ARTICLE
Claudia Wellbrock, Christin Weisser, Eva Geissinger, Jakob Troppmair, Manfred Schartl
Malignant melanoma is a cancer whose incidence is rising rapidly, but the mechanism by which normal melanocytes become malignant in vivo is still little understood. In the course of melanoma progression, a fraction of cells often becomes depigmented, which reflects the loss of the balance between mitogenic activities and differentiation in those pigment cells. A key factor involved in differentiation in pigment cells is mitogen-activated protein kinase (MAPK). However, because both activation and inhibition of MAPK signaling is known to correlate with differentiation, its function in pigment cells is still unclear...
February 22, 2002: Journal of Biological Chemistry
https://read.qxmd.com/read/10848967/activation-of-phosphatidylinositol-3-kinase-by-a-complex-of-p59fyn-and-the-receptor-tyrosine-kinase-xmrk-is-involved-in-malignant-transformation-of-pigment-cells
#36
JOURNAL ARTICLE
C Wellbrock, M Schartl
Malignant melanoma in the fish Xiphophorus is induced by overexpression of the Xmrk-oncogene, encoding a subclass I receptor tyrosine kinase. The mutationally activated Xmrk protein triggers constitutive mitogenic signalling in fish melanoma cells. In recent studies we showed that in melanoma cells phosphatidylinositol (PtdIns) 3-kinase, as well as p59fyn, has elevated levels of kinase activity. Both bind directly to different phosphotyrosine residues in the Xmrk receptor C-terminus through their SH2 domains...
June 2000: European Journal of Biochemistry
https://read.qxmd.com/read/10613822/signals-leading-to-apoptosis-dependent-inhibition-of-neovascularization-by-thrombospondin-1
#37
JOURNAL ARTICLE
B Jiménez, O V Volpert, S E Crawford, M Febbraio, R L Silverstein, N Bouck
Thrombospondin-1 (TSP-1) is a naturally occurring inhibitor of angiogenesis that limits vessel density in normal tissues and curtails tumor growth. Here, we show that the inhibition of angiogenesis in vitro and in vivo and the induction of apoptosis by thrombospondin-1 all required the sequential activation of CD36, p59fyn, caspase-3 like proteases and p38 mitogen-activated protein kinases. We also detected increased endothelial cell apoptosis in situ at the margins of tumors in mice treated with thrombospondin-1...
January 2000: Nature Medicine
https://read.qxmd.com/read/10091608/multiple-binding-sites-in-the-growth-factor-receptor-xmrk-mediate-binding-to-p59fyn-grb2-and-shc
#38
JOURNAL ARTICLE
C Wellbrock, M Schartl
Melanoma formation in Xiphoporus is initiated by overexpression of the EGFR-related receptor tyrosine kinase Xmrk (Xiphoporus melanoma receptor kinase). This receptor is activated in fish melanoma as well as in a melanoma-derived cell line (PSM) resulting in constitutive Xmrk-mediated mitogenic signaling. In order to define the underlying signaling pathway(s), triggered by the activated Xmrk receptor, we attempted to identify its physiological substrates. Examination of the Xmrk carboxyterminus for putative tyrosine autophosphorylation sites revealed the presence of potential binding motifs for GRB2 as well as for Shc...
February 1999: European Journal of Biochemistry
https://read.qxmd.com/read/9815928/alterations-in-t-cell-receptor-and-signal-transduction-molecules-in-melanoma-patients
#39
JOURNAL ARTICLE
A H Zea, B D Curti, D L Longo, W G Alvord, S L Strobl, H Mizoguchi, S P Creekmore, J J O'Shea, G C Powers, W J Urba
We have recently described molecular changes in T cells from tumor-bearing patients that are associated with depressed immune function. The present work investigates changes in T-cell signal transduction proteins including the T-cell receptor-zeta (TCR-zeta) chain and receptor-associated tyrosine kinases in patients with metastatic malignant melanoma. A marked decrease in the expression of the TCR-zeta chain was observed in the peripheral blood T cells of 19 (43%) of 44 patients. Decreases in several tyrosine kinases were found in 12 (57%) of 21 patients tested...
November 1995: Clinical Cancer Research
https://read.qxmd.com/read/9690455/ex-vivo-activation-of-tumor-draining-lymph-node-t-cells-reverses-defects-in-signal-transduction-molecules
#40
JOURNAL ARTICLE
J Liu, J Finke, J C Krauss, S Shu, G E Plautz
The adoptive transfer of tumor-draining lymph node (LN) T cells activated ex vivo with anti-CD3 and interleukin 2 (IL-2) mediates the regression of the poorly immunogenic murine melanoma D5. The efficacy of the activated LN cells is augmented when the sensitizing tumor is a genetically modified variant (designated D5G6) that secretes granulocyte/macrophage-colony-stimulating factor. In contrast to anti-CD3/IL-2-activated LN cells, adoptive transfer of freshly isolated tumor-draining LN T cells has no therapeutic activity...
July 1998: Cancer Immunology, Immunotherapy: CII
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