Bruton tyrosine kinase is essential for botrocetin/VWF-induced signaling and GPIb-dependent thrombus formation in vivo

Liu, Junling; Fitzgerald, Malinda E.C.; Berndt, Michael C.; Jackson, Carl W.; Gartner, T. Kent

doi:10.1182/blood-2006-01-011817

Cited by 129 publications

(119 citation statements)

References 57 publications

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“…[25][26][27] As described by others, the VWF-GP1bIX interaction induces platelet activation through this signaling pathway, leading to the integrin activation and stabilization of platelet adhesion and aggregation. [27][28][29] Our observation also describes a similar signaling for the Hb in inducing platelet activation upon binding to GP1bα. This Hb-GP1bα interaction initiated a change in platelet shape ( Figure 2G), granule secretion ( Figure 1A) and the inside out signaling process ( Figure 2E), and activated integrin GPIIb-IIIa ( Figure 1B).…”

Section: Discussionmentioning

confidence: 59%

Hemoglobin interaction with GP1b induces platelet activation and apoptosis: a novel mechanism associated with intravascular hemolysis

et al. 2015

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Section: Discussionmentioning

confidence: 59%

Hemoglobin interaction with GP1b induces platelet activation and apoptosis: a novel mechanism associated with intravascular hemolysis

et al. 2015

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“…Platelet activation by vWF, the other activation pathway that is affected by ibrutinib treatment 20, also involves BTK 80. So far, no role for TEC has been described in this process, but it does not seem to compensate for absent BTK, because no phosphorylation of PLC γ 2 was found in platelets from BTK‐deficient mice after vWF stimulation, and no stable vWF‐dependent thrombus formation was observed in vivo in these mice 81. A recent report showed the importance of BTK and TEC in CLEC‐2 receptor‐mediated platelet activation 82.…”

Section: Consequences Of Ibrutinib Treatment Not Related To B Cellsmentioning

confidence: 99%

Targets for Ibrutinib Beyond B Cell Malignancies

et al. 2015

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Ibrutinib (Imbruvica™) is an irreversible, potent inhibitor of Bruton's tyrosine kinase (BTK). Over the last few years, ibrutinib has developed from a promising drug candidate to being approved by FDA for the treatment of three B cell malignancies, a truly remarkable feat. Few, if any medicines are monospecific and ibrutinib is no exception; already during ibrutinib's initial characterization, it was found that it could bind also to other kinases. In this review, we discuss the implications of such interactions, which go beyond the selective effect on BTK in B cell malignancies. In certain cases, the outcome of ibrutinib treatment likely results from the combined inhibition of BTK and other kinases, causing additive or synergistic, effects. Conversely, there are also examples when the clinical outcome seems unrelated to inhibition of BTK. Thus, more specifically, adverse effects such as enhanced bleeding or arrhythmias could potentially be explained by different interactions. We also predict that during long‐term treatment bone homoeostasis might be affected due to the inhibition of osteoclasts. Moreover, the binding of ibrutinib to molecular targets other than BTK or effects on cells other than B cell‐derived malignancies could be beneficial and result in new indications for clinical applications.

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“…After removal of the filter paper, the exposed area was thoroughly rinsed with isotonic saline. Blood flow was monitored by using a laser Doppler system (Trimflo; Vasamedics, Eden Prairie, MN) connected to a BPM 2 blood perfusion monitor (Vasamedics) interfaced via an analogue to digital output with software from PowerLab System (AD Instruments, Castle Hill, Australia) (47).…”

Section: Methodsmentioning

confidence: 99%

Platelet glycoprotein Ibα supports experimental lung metastasis

Jain

Zuka

Liu

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The platelet paradigm in hemostasis and thrombosis involves an initiation step that depends on platelet membrane receptors binding to ligands on a damaged or inflamed vascular surface. Once bound to the surface, platelets provide a unique microenvironment supporting the accumulation of more platelets and the elaboration of a fibrin-rich network produced by coagulation factors. The platelet-specific receptor glycoprotein (GP) Ib-IX, is critical in this process and initiates the formation of a platelet-rich thrombus by tethering the platelet to a thrombogenic surface. A role for platelets beyond the hemostasis/thrombosis paradigm is emerging with significant platelet contributions in both tumorigenesis and inflammation. We have established congenic (N10) mouse colonies (C57BL/6J) with dysfunctional GP Ib-IX receptors in our laboratory that allow us an opportunity to examine the relevance of platelet GP Ib-IX in syngeneic mouse models of experimental metastasis. Our results demonstrate platelet GP Ib-IX contributes to experimental metastasis because a functional absence of GP Ib-IX correlates with a 15-fold reduction in the number of lung metastatic foci using B16F10.1 melanoma cells. The results demonstrate that the extracellular domain of the ␣-subunit of GP Ib is the structurally relevant component of the GP Ib-IX complex contributing to metastasis. Our results support the hypothesis that platelet GP Ib-IX functions that support normal hemostasis or pathologic thrombosis also contribute to tumor malignancy.adhesion ͉ tumor ͉ hemostasis ͉ knockout ͉ melanoma C irculating blood platelets have an inherent adhesive potential long recognized as essential for hemostasis and thrombosis. Beyond the platelet paradigm for blood clotting and thrombosis, it is becoming apparent that the platelet's adhesive potential influences pathological events outside its role in hemostasis. Indeed, emerging hypotheses suggest the platelet paradigm in hemostasis and thrombosis, an accumulation of platelets and the elaboration of a fibrin matrix, may provide a mechanism for circulating tumor cells to metastasize. Experimental proof that platelets effect tumor metastasis was provided in models where an experimental lowering of circulating platelet counts reduced metastasis (1-3).Evidence suggests that carcinoma cells entering the circulation interact with both platelets and leukocytes to form tumor cell aggregates (1, 4). Data have suggested one mechanism linking the platelet to metastasis is a platelet ''cloak'' surrounding the tumor cell and protecting the tumor cell from immune surveillance (5, 6). Tumorigenesis has been linked to several molecules essential for blood coagulation and normal platelet function. These include thrombin, tissue factor, platelet P-selectin, fibrinogen, and lysophosphatidic acid (3,4,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Together, these results suggest that platelets and their procoagulant activity support tumor metastasis, possibly by aiding tumor cells to lodge in the microvasculature and either extravasate...

show abstract

Bruton tyrosine kinase is essential for botrocetin/VWF-induced signaling and GPIb-dependent thrombus formation in vivo

Cited by 129 publications

References 57 publications

Hemoglobin interaction with GP1b induces platelet activation and apoptosis: a novel mechanism associated with intravascular hemolysis

Hemoglobin interaction with GP1b induces platelet activation and apoptosis: a novel mechanism associated with intravascular hemolysis

Targets for Ibrutinib Beyond B Cell Malignancies

Platelet glycoprotein Ibα supports experimental lung metastasis

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