Induction of Disabled-2 Gene during Megakaryocyte Differentiation of K562 Cells

Tseng, Ching Ping; Huang, Ching Hui; Tseng, Ching Chung; Lin, Mei-Hui; Hsieh, Jer Tsong; Tseng, Chao‐Hsiung

doi:10.1006/bbrc.2001.5133

Cited by 40 publications

(33 citation statements)

References 18 publications

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“…Moreover, TFs involved in epigenetic events, such as Hmgn3 and Prmt5, were up-regulated by the VPA ϩ Li treatment. 36 In contrast, most of the down-regulated targets were correlated with cellular differentiation, including known TFs for myeloid (Erg1/2, Junb), 37,38 erythroid/megakaryocyte (Dab2), 39 and lymphoid (Irf5, Nfkbia) 40,41 differentiation. TFs up-regulated by the treatment, showing a negative correlation with differentiation-associated TFs, seem to be especially interesting as targets for differentiation-preventing agents.…”

Section: Vpa and LI Delay Hspc Differentiation 3055mentioning

confidence: 98%

The combination of valproic acid and lithium delays hematopoietic stem/progenitor cell differentiation

Walasek¹,

Bystrykh²,

Boom

et al. 2012

Blood

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Despite increasing knowledge on the regulation of hematopoietic stem/progenitor cell (HSPC) self-renewal and differentiation, in vitro control of stem cell fate decisions has been difficult. The ability to inhibit HSPC commitment in culture may be of benefit to cell therapy protocols. Small molecules can serve as tools to manipulate cell fate decisions. Here, we tested 2 small molecules, valproic acid (VPA) and lithium (Li), to inhibit differentiation. HSPCs exposed to VPA and Li during differentiation-inducing culture preserved an immature cell phenotype, provided radioprotection to lethally irradiated recipients, and enhanced in vivo repopulating potential. Anti-differentiation effects of VPA and Li were observed also at the level of committed progenitors, where VPA re-activated replating activity of common myeloid progenitor and granulocyte macrophage progenitor cells.

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Section: Vpa and LI Delay Hspc Differentiation 3055mentioning

confidence: 98%

The combination of valproic acid and lithium delays hematopoietic stem/progenitor cell differentiation

Walasek¹,

Bystrykh²,

Boom

et al. 2012

Blood

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“…Indeed, there are contrasting reports as to whether p38MAPK is activated in established megakaryocytic cell lines (K562 and CHRF-288) and in primary MKs in response to phorbol ester and TPO [74,75,78,84,[107][108][109]. Nevertheless, the role of p38MAPK in MK differentiation has been investigated using specific inhibitors, SB203580 and SB202190 as summarized in Table 1.…”

Section: The P38 Pathway and Megakaryocyte Differentiationmentioning

confidence: 99%

The mitogen‐activated protein kinase signaling pathways: role in megakaryocyte differentiation

Séverin

Ghevaert

Mazharian

2010

Journal of Thrombosis and Haemostasis

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“…Accordingly, DAB2 acts to control a variety of cellular processes including growth factor and hormone signaling, endocytosis and cell-adhesive function (Xu et al, 1998;Inoue et al, 2002;Morris et al, 2002;Kowanetz et al, 2003;Zhou et al, 2003). In the hematopoietic system, DAB2 is abundantly expressed in human platelets (Huang et al, 2004) and is upregulated through platelet-derived growth factor (PDGF) autocrine signaling (Tseng et al, 2005) during megakaryocytic differentiation of human leukemic cell lines and CD34 + hematopoietic pluripotent stem cells (Tseng et al, 2001;Tseng et al, 2003;Huang et al, 2004). DAB2 negatively regulates ␣IIb␤3-integrin-mediated fibrinogen adhesion and cell signaling in a S24-phosphorylation-dependent manner that promotes DAB2 membrane translocation and the subsequent interaction with the ␤3 integrin cytoplasmic tail (Huang et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Disabled-2 is a novel αIIb-integrin-binding protein that negatively regulates platelet-fibrinogen interactions and platelet aggregation

Huang

Cheng

Stern

et al. 2006

Journal of Cell Science

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Platelet aggregation plays a pivotal role in the haemostatic process and is involved in the pathological counterpart of arterial thrombosis. We have shown that the adapter protein disabled-2 (DAB2) is expressed abundantly in platelets. In this study, DAB2 was found to distribute in the platelet ␣ ␣-granules and was released from the granular compartment upon platelet activation. The secreted DAB2 binds to the extracellular region of ␣ ␣IIb␤ ␤3 integrin on the platelet surface through the phosphotyrosine-binding domain. The DAB2-platelet interactions result in the inhibition of agonist-induced platelet aggregation with the exception of thrombin, a DAB2 protease that renders DAB2 inactive. Biochemical and mutational analysis revealed that the DAB2 cell-adhesion Arg-Gly-Asp (RGD) motif (amino acid residues 64-66) and the ␣ ␣IIb-integrin-fibrinogenbinding region (amino acid residues 171-464) are important for the DAB2-platelet interactions. Such interactions compete for the binding of ␣ ␣IIb integrin with fibrinogen and provide a mechanism for DAB2 to inhibit platelet aggregation. Accordingly, the synthetic RGD-motifcontaining DAB2 peptide PDARGDKM also elicited antiplatelet aggregation activity. These findings demonstrate for the first time that DAB2 is an ␣ ␣IIb-integrin-binding protein that plays a novel role in the control of plateletfibrinogen interactions and platelet aggregation.Key words: Disabled-2, Fibrinogen, ␣IIb␤3 Integrin, Platelet aggregation, RGD motif SummaryDisabled-2 is a novel ␣ ␣IIb-integrin-binding protein that negatively regulates platelet-fibrinogen interactions and platelet aggregation

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Induction of Disabled-2 Gene during Megakaryocyte Differentiation of K562 Cells

Cited by 40 publications

References 18 publications

The combination of valproic acid and lithium delays hematopoietic stem/progenitor cell differentiation

The combination of valproic acid and lithium delays hematopoietic stem/progenitor cell differentiation

The mitogen‐activated protein kinase signaling pathways: role in megakaryocyte differentiation

Disabled-2 is a novel αIIb-integrin-binding protein that negatively regulates platelet-fibrinogen interactions and platelet aggregation

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