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https://www.readbyqxmd.com/read/27766053/new-horizon-in-platelet-function-with-special-reference-to-a-recently-found-molecule-clec-2
#1
Yukio Ozaki, Shogo Tamura, Katsue Suzuki-Inoue
Platelets play a key role in the pathophysiological processes of hemostasis and thrombus formation. However, platelet functions beyond thrombosis and hemostasis have been increasingly identified in recent years. A large body of evidence now exists which suggests that platelets also play a key role in inflammation, immunity, malignancy, and furthermore in organ development and regeneration, such as the liver. We have recently identified CLEC-2 on the platelet membrane, which induces intracellular activation signals upon interaction of a snake venom, rhodocytin...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27766044/anti-thrombotic-agents-derived-from-snake-venom-proteins
#2
Tur-Fu Huang, Chun-Chieh Hsu, Yu-Ju Kuo
Snake venoms affect blood coagulation and platelet function in a complex manner. However, two classes of venom proteins, snaclecs and disintegrins have been shown to specifically target receptors including GPIb, α2β1, GPVI, CLEC-2 and integrins αIIbβ3, αvβ3, α5β1 expressed on platelets, endothelial cells, phagocytes, tumor cells, thus affecting cell-matrices and cell-cell interactions. Here, we focus on disintegrins, a class of low molecular mass Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing, cysteine-rich polypeptide derived from various viper snake venoms...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27564251/lpmab-19-recognizes-sialylated-o-glycan-on-thr76-of-human-podoplanin
#3
Satoshi Ogasawara, Mika K Kaneko, Yukinari Kato
Human podoplanin (hPDPN) is expressed in lymphatic vessels, pulmonary type-I alveolar cells, and renal glomerulus. The hPDPN/C-type lectin-like receptor-2 (CLEC-2) interaction is involved in platelet aggregation and cancer metastasis. High expression of hPDPN in cancer cells or cancer-associated fibroblasts (CAFs) leads to a poor prognosis for cancer patients. In our previous research, we reported on several anti-hPDPN monoclonal antibodies (mAbs), including LpMab-2, LpMab-3, LpMab-7, LpMab-9, LpMab-12, LpMab-13, and LpMab-17 of mouse IgG1 subclass, which were produced using CasMab technology...
August 26, 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/27564117/high-clec-2-expression-associates-with-unfavorable-postoperative-prognosis-of-patients-with-clear-cell-renal-cell-carcinoma
#4
Ying Xiong, Li Liu, Yu Xia, Jiajun Wang, Wei Xi, Qi Bai, Yang Qu, Qilai Long, Jiejie Xu, Jianming Guo
We enrolled a total of 277 patients who received nephrectomy due to clear cell renal cell carcinoma (ccRCC) in Zhongshan Hospital from Jan 2005 to Jun 2007. Immunohistochemistry was performed to evaluate the impact of CLEC-2 positive cell infiltration on the overall survival (OS) and recurrence-free survival (RFS) of patients with ccRCC. Kaplan-Meier analysis showed that high CLEC-2 positive cell infiltration in tumor tissue indicated poorer OS and RFS (OS, p < 0.001; RFS, p = 0.002). High CLEC-2 positive cell infiltration is also an independent risk factor for OS and RFS in multivariate analyses (OS, p = 0...
August 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27443248/e3-ubiquitin-ligase-chip-interacts-with-c-type-lectin-like-receptor-clec-2-and-promotes-its-ubiquitin-proteasome-degradation
#5
Miaomiao Shao, Lili Li, Shushu Song, Weicheng Wu, Peike Peng, Caiting Yang, Mingming Zhang, Fangfang Duan, Dongwei Jia, Jie Zhang, Hao Wu, Ran Zhao, Lan Wang, Yuanyuan Ruan, Jianxin Gu
C-type lectin-like receptor 2 (CLEC-2) was originally identified as a member of non-classical C-type lectin-like receptors in platelets and immune cells. Activation of CLEC-2 is involved in thrombus formation, lymphatic/blood vessel separation, platelet-mediated tumor metastasis and immune response. Nevertheless, the regulation of CLEC-2 expression is little understood. In this study, we identified that the C terminus of Hsc70-interacting protein (CHIP) interacted with CLEC-2 by mass spectrometry analysis, and CHIP decreased the protein expression of CLEC-2 through lysine-48-linked ubiquitination and proteasomal degradation...
October 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27385789/lymphovenous-hemostasis-and-the-role-of-platelets-in-regulating-lymphatic-flow-and-lymphatic-vessel-maturation
#6
REVIEW
John D Welsh, Mark L Kahn, Daniel T Sweet
Aside from the established role for platelets in regulating hemostasis and thrombosis, recent research has revealed a discrete role for platelets in the separation of the blood and lymphatic vascular systems. Platelets are activated by interaction with lymphatic endothelial cells at the lymphovenous junction, the site in the body where the lymphatic system drains into the blood vascular system, resulting in a platelet plug that, with the lymphovenous valve, prevents blood from entering the lymphatic circulation...
September 1, 2016: Blood
https://www.readbyqxmd.com/read/27380308/specific-detection-of-dog-podoplanin-expressed-in-renal-glomerulus-by-a-novel-monoclonal-antibody-pmab-38-in-immunohistochemistry
#7
Ryusuke Honma, Mika K Kaneko, Satoshi Ogasawara, Yuki Fujii, Satoru Konnai, Michiaki Takagi, Yukinari Kato
Podoplanin (PDPN) is expressed in several normal tissues including podocytes of renal glomerulus, lymphatic endothelial cells (LECs), and type I alveolar cells of lung. PDPN activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelets. Many monoclonal antibodies (mAbs) against human PDPN, mouse PDPN, rat PDPN, rabbit PDPN, and bovine PDPN have been established; antidog PDPN (dPDPN) mAbs have not been developed. Herein, we immunized mice with the recombinant proteins of dPDPN and developed anti-dPDPN mAbs...
August 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/27328060/establishment-of-mouse-monoclonal-antibody-lpmab-13-against-human-podoplanin
#8
Satoshi Ogasawara, Mika K Kaneko, Ryusuke Honma, Hiroharu Oki, Yuki Fujii, Michiaki Takagi, Hiroyoshi Suzuki, Yukinari Kato
Podoplanin (PDPN)/Aggrus is a type-I transmembrane sialoglycoprotein, which possesses a platelet aggregation-stimulating (PLAG) domain. The O-glycosylation on Thr52 of human PDPN (hPDPN) is critical for the interaction of hPDPN with C-type lectin-like receptor-2 (CLEC-2), resulting in platelet aggregation. Many anti-hPDPN monoclonal antibodies (MAbs) against PLAG domains and non-PLAG domains have been established; however, mouse anti-PLAG2/3 MAb, the epitope of which is consistent with rat anti-PLAG2/3 MAb NZ-1, has not been established...
June 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/27267652/pmab-44-detects-bovine-podoplanin-in-immunohistochemistry
#9
Ryusuke Honma, Satoshi Ogasawara, Mika K Kaneko, Yuki Fujii, Hiroharu Oki, Takuro Nakamura, Michiaki Takagi, Satoru Konnai, Yukinari Kato
Podoplanin (PDPN)/Aggrus is a type I transmembrane O-glycoprotein, which is expressed in several normal tissues including podocytes of kidney and lymphatic endothelial cells. PDPN activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelet; however, only bovine PDPN (bovPDPN) does not possess the platelet-aggregating activity. Although many monoclonal antibodies (mAbs) against human PDPN, mouse PDPN, rat PDPN, and rabbit PDPN have been established, anti-bovPDPN mAbs have not been developed...
June 7, 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/27148766/establishment-of-mouse-monoclonal-antibody-lpmab-13-against-human-podoplanin
#10
Satoshi Ogasawara, Mika K Kaneko, Ryusuke Honma, Hiroharu Oki, Yuki Fujii, Michiaki Takagi, Hiroyoshi Suzuki, Yukinari Kato
Podoplanin (PDPN)/Aggrus is a type-I transmembrane sialoglycoprotein, which possesses a platelet aggregation-stimulating (PLAG) domain. The O-glycosylation on Thr52 of human PDPN (hPDPN) is critical for the interaction of hPDPN with C-type lectin-like receptor-2 (CLEC-2), resulting in platelet aggregation. Many anti-hPDPN monoclonal antibodies (MAbs) against PLAG domains and non-PLAG domains have been established; however, mouse anti-PLAG2/3 MAb, the epitope of which is consistent with rat anti-PLAG2/3 MAb NZ-1, has not been established...
May 5, 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/27034419/clec-2-and-podoplanin-partners-again
#11
COMMENT
Jianxin Fu, Lijun Xia
In this issue of Blood, Tamura et al reveal a novel function for podoplanin on periarteriolar stromal cells in the bone marrow: promoting megakaryocyte growth and proplatelet formation by interaction with C-type lectin-like receptor 2 (CLEC-2).
March 31, 2016: Blood
https://www.readbyqxmd.com/read/27031228/lpmab-12-established-by-casmab-technology-specifically-detects-sialylated-o-glycan-on-thr52-of-platelet-aggregation-stimulating-domain-of-human-podoplanin
#12
Yukinari Kato, Satoshi Ogasawara, Hiroharu Oki, Polina Goichberg, Ryusuke Honma, Yuki Fujii, Mika K Kaneko
Podoplanin (PDPN), also known as Aggrus, possesses three tandem repeat of platelet aggregation-stimulating (PLAG) domains in its N-terminus. Among the PLAG domains, sialylated O-glycan on Thr52 of PLAG3 is essential for the binding to C-type lectin-like receptor-2 (CLEC-2) and the platelet-aggregating activity of human PDPN (hPDPN). Although various anti-hPDPN monoclonal antibodies (mAbs) have been generated, no specific mAb has been reported to target the epitope containing glycosylated Thr52. We recently established CasMab technology to develop mAbs against glycosylated membrane proteins...
2016: PloS One
https://www.readbyqxmd.com/read/26937552/novel-monoclonal-antibody-lpmab-17-developed-by-casmab-technology-distinguishes-human-podoplanin-from-monkey-podoplanin
#13
Yukinari Kato, Satoshi Ogasawara, Hiroharu Oki, Ryusuke Honma, Michiaki Takagi, Yuki Fujii, Takuro Nakamura, Noriko Saidoh, Hazuki Kanno, Mitsuo Umetsu, Satoshi Kamata, Hiroshi Kubo, Mitsuhiro Yamada, Yoshihiko Sawa, Kei-Ichi Morita, Hiroyuki Harada, Hiroyoshi Suzuki, Mika Kato Kaneko
Podoplanin (PDPN) is a type-I transmembrane sialoglycoprotein, which possesses a platelet aggregation-stimulating (PLAG) domain in its N-terminus. Among the three PLAG domains, O-glycan on Thr52 of PLAG3 is critical for the binding with C-type lectin-like receptor-2 (CLEC-2) and is essential for platelet-aggregating activity of PDPN. Although many anti-PDPN monoclonal antibodies (mAbs) have been established, almost all mAbs bind to PLAG domains. We recently established CasMab technology to produce mAbs against membranous proteins...
April 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/26800051/partially-defective-store-operated-calcium-entry-and-hem-itam-signaling-in-platelets-of-serotonin-transporter-deficient-mice
#14
Karen Wolf, Attila Braun, Elizabeth J Haining, Yu-Lun Tseng, Peter Kraft, Michael K Schuhmann, Sanjeev K Gotru, Wenchun Chen, Heike M Hermanns, Guido Stoll, Klaus-Peter Lesch, Bernhard Nieswandt
BACKGROUND: Serotonin (5-hydroxytryptamin, 5-HT) is an indolamine platelet agonist, biochemically derived from tryptophan. 5-HT is secreted from the enterochromaffin cells into the gastrointestinal tract and blood. Blood 5-HT has been proposed to regulate hemostasis by acting as a vasoconstrictor and by triggering platelet signaling through 5-HT receptor 2A (5HTR2A). Although platelets do not synthetize 5-HT, they take 5-HT up from the blood and store it in their dense granules which are secreted upon platelet activation...
2016: PloS One
https://www.readbyqxmd.com/read/26796360/podoplanin-positive-periarteriolar-stromal-cells-promote-megakaryocyte-growth-and-proplatelet-formation-in-mice-by-clec-2
#15
Shogo Tamura, Katsue Suzuki-Inoue, Nagaharu Tsukiji, Toshiaki Shirai, Tomoyuki Sasaki, Makoto Osada, Kaneo Satoh, Yukio Ozaki
Megakaryopoiesis is the hierarchical differentiation of hematopoietic stem cells into megakaryocytes. Differentiating megakaryocytes undergo maturation characterized by endomitosis and produce numerous platelets through proplatelet formation. C-type lectin-like receptor 2 (CLEC-2) is a podoplanin (PDPN) receptor mainly expressed on platelets and megakaryocytes. Deletion of platelet/megakaryocyte CLEC-2 causes thrombocytopenia in mice; however, its contribution to megakaryopoiesis remains unknown. Here, we show that megakaryopoiesis is promoted through the CLEC-2/PDPN interaction in the vicinity of arterioles in the bone marrow (BM)...
March 31, 2016: Blood
https://www.readbyqxmd.com/read/26788987/establishment-of-novel-monoclonal-antibody-pmab-32-against-rabbit-podoplanin
#16
Ryusuke Honma, Yuki Fujii, Satoshi Ogasawara, Hiroharu Oki, Xing Liu, Takuro Nakamura, Mika K Kaneko, Michiaki Takagi, Yukinari Kato
Podoplanin (PDPN) is a type I transmembrane O-glycoprotein, which is known as a specific lymphatic marker. PDPN activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelet. PDPN is also expressed in several normal tissues, including podocytes and type I alveolar cells. Although many monoclonal antibodies (MAbs) against human PDPN (hPDPN), mouse PDPN (mPDPN), and rat PDPN (rPDPN) have been established, useful antibodies against rabbit PDPN (rabPDPN) have not been developed...
February 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/26684030/targeting-a-novel-domain-in-podoplanin-for-inhibiting-platelet-mediated-tumor-metastasis
#17
Takaya Sekiguchi, Ai Takemoto, Satoshi Takagi, Kazuki Takatori, Shigeo Sato, Miho Takami, Naoya Fujita
Podoplanin/Aggrus is a sialoglycoprotein expressed in various cancers. We previously identified podoplanin as a key factor in tumor-induced platelet aggregation. Podoplanin-mediated platelet aggregation enhances tumor growth and metastasis by secreting growth factors and by forming tumor emboli in the microvasculature. Thus, precise analysis of the mechanisms of podoplanin-mediated platelet aggregation is critical for developing anti-tumor therapies. Here we report the discovery of a novel platelet aggregation-inducing domain, PLAG4 (81-EDLPT-85)...
January 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/26683179/development-of-sensitive-monoclonal-antibody-pmab-2-against-rat-podoplanin
#18
Hiroharu Oki, Ryusuke Honma, Satoshi Ogasawara, Yuki Fujii, Xing Liu, Michiaki Takagi, Mika K Kaneko, Yukinari Kato
Podoplanin (PDPN) is a platelet aggregation-inducing factor, which is known as an endogenous ligand of C-type lectin-like receptor-2 (CLEC-2). PDPN is also expressed in several normal tissues, such as lung type I alveolar cells and kidney podocytes. Although many monoclonal antibodies (MAbs) against human PDPN (hPDPN) or mouse PDPN (mPDPN) have been established, anti-rat PDPN (rPDPN) MAbs, especially against platelet aggregation-stimulating (PLAG) domain (29-54 amino acids) of rPDPN, have not been developed...
December 2015: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/26642853/correction-clec-2-in-megakaryocytes-is-critical-for-maintenance-of-hematopoietic-stem-cells-in-the-bone-marrow
#19
Ayako Nakamura-Ishizu, Keiyo Takubo, Hiroshi Kobayashi, Katsue Suzuki-Inoue, Toshio Suda
No abstract text is available yet for this article.
December 14, 2015: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/26619766/dextran-sulfate-triggers-platelet-aggregation-via-direct-activation-of-pear1
#20
Christophe Vandenbriele, Yi Sun, Maarten Criel, Katrien Cludts, Soetkin Van Kerckhoven, Benedetta Izzi, Thomas Vanassche, Peter Verhamme, Marc F Hoylaerts
UNLABELLED: Dextran sulfate (DxS; Mr 500 kD) induces fibrinogen receptor (αIIbβ3) activation via CLEC-2/Syk signaling and via a Syk-independent SFK/PI3K/Akt-dependent tyrosine kinase pathway in human and murine platelets. The platelet surface receptor, responsible for the DxS-induced Syk-independent Akt-activation, has hitherto not been identified. We found that DxS elicited a concentration-dependent aggregation of human platelets resulting from direct PEAR1 activation by DxS. Blocking the PEAR1 receptor, in combination with a selective Syk-inhibitor, completely abrogated the DxS-driven platelet aggregation...
June 2016: Platelets
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