2007年11月13日 · Here, we show that the combined deficiency of Rac1 and Rac2 Rho GTPases significantly attenuates p210-BCR-ABL-induced proliferation in vitro and MPD in vivo and confirm Rac as a therapeutic target in p210-BCR-ABL disease using a …

2019年2月8日 · Our genetic data suggest Abl-Abi and Rac1-SCAR signaling restrain synaptic growth via inhibition of presynaptic BMP signaling. Importantly, we show that Gbb induces synaptic macropinocytosis in...

2022年9月16日 · The Rho-family GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization in many essential processes. Rac1 binds to WRC at two distinct...

2018年2月12日 · In hematological malignancies, studies have shown that Rac1 GTPase activated by BCR-ABL represented a novel target in chronic myeloid leukemia. Additionally, Rac1 inhibition delays the...

We have recently shown in a murine model that deficiency of the Rho GTPases Rac1 and Rac2 significantly reduces p210-BCR-ABL-mediated proliferation in vitro and myeloproliferative disease in vivo, suggesting Rac as a potential therapeutic target in p210-BCR-ABL-induced disease.

2019年2月8日 · Our genetic data suggest Abl-Abi and Rac1-SCAR signaling restrain synaptic growth via inhibition of presynaptic BMP signaling. Importantly, we show that Gbb induces synaptic macropinocytosis in a BMPR-dependent mechanism, with induction impaired by disrupting both Abl-Abi and Rac1-SCAR pathways.

Here we show that SOS1 is tyrosine phosphorylated on Y1196 by ABL. Phosphorylation of Y1196 controls SOS1 inter-molecular interaction, is required to promote the exchange of nucleotides on RAC in vitro and for platelet-derived growth factor (PDGF) activation of RAC- and RAC-dependent actin remodeling and cell migration.

We demonstrate in a murine model of p210-BCR-ABL-induced MPD that gene targeting of Rac1 and Rac2 significantly delays or abrogates disease development. Attenuation of the disease phenotype is associated with severely diminished p210-BCR-ABL-induced downstream signaling in primary hematopoietic cells.

2002年4月5日 · Bcr-Abl transduced primary bone marrow from Vav knock-out mice showed reduced proliferation in a culture cell transformation assay compared with wild-type bone marrow. These results suggest, that Bcr-Abl utilizes Vav as a guanine nucleotide exchange factor to activate Rac-1 in a process that involves a folding mechanism of the Vav C terminus.

2011年9月27日 · Previous studies have shown that Abl kinases can promote or attenuate Rap1 activation dependent on the cellular context. Endogenous Abl kinase activity is required for Rap1 activation and increased integrin affinity in response to engagement of the T cell receptor (TCR) .