Formation of long and winding nuclear F-actin bundles by nuclear c-Abl tyrosine kinase

Aoyama, Kazumasa; Yuki, Ryuzaburo; Horiike, Yasuyoshi; Kubota, Sho; Yamaguchi, Noritaka; Morii, Mariko; Ishibashi, Keiichiro; Nakayama, Yuji; Kuga, Tetsurō; Hashimoto, Yuki; Tomonaga, Takeshi; Yamaguchi, Naoto

doi:10.1016/j.yexcr.2013.09.003

Cited by 21 publications

(24 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To prevent dephosphorylation of proteins, Na 3 VO 4 is added at a final concentration of 10 mM to both immunoprecipitation buffer and SDS sample buffer, and the samples heated at 95°C for 5 min in SDS sample buffer are immediately kept at 4°C and subjected to SDS-PAGE without freeze-thawing (see also "Experimental Procedures"). Thus, by minimizing inactivation of Na 3 VO 4 , we succeeded in finding quite a few tyrosine-phosphorylated proteins by our phosphoproteomic analysis (5,25). Furthermore, we were successfully able to detect Src-mediated tyrosine phosphorylation of endogenous Ku70 in the presence of pervanadate, a highly potent protein-tyrosine phosphatase inhibitor (Fig.…”

Section: Discussionmentioning

confidence: 86%

“…The mechanism of Src-mediated suppression of apoptosis through Src substrates still remains poorly understood, possibly because protein-tyrosine phosphorylation is extremely unstable within cells. We, therefore, assume that phosphorylation levels of substrates are very rapidly regulated by a balance of the activities between tyrosine kinases and tyrosine phosphatases, like ON/OFF switching in a microprocessor (5,(22)(23)(24)(25)(26)(27)57). Nonetheless, carefully using a high dose of the potent tyrosine phosphatase inhibitor Na 3 VO 4 , we are able to detect tyrosine phosphorylation of endogenous proteins and have shown the significance of tyrosine-phosphorylated substrates (5,24,26,27).…”

Section: Discussionmentioning

confidence: 99%

“…To explore in detail the roles of protein-tyrosine phosphorylation in cell functions, we recently performed phosphoproteomic analyses (5,25) and revealed novel roles for tyrosine phosphorylation of nuclear proteins, such as the heterochromatin protein KAP1 (KRAB-associated protein 1)/TIF1␤/TRIM28 (5), the transcription factors JunB (26) and FoxA1 (27), and the chromatinassociated protein AKAP8 (A-kinase anchoring protein 8) (24).…”

mentioning

confidence: 99%

“…Western Blotting and Immunoprecipitation-Western blotting was performed with enhanced chemiluminescence (Millipore) as described previously (14,24,25). Whole cell lysates prepared in Laemmli SDS sample buffer were subjected to SDSpolyacrylamide gel electrophoresis and electrotransferred onto polyvinylidene difluoride membranes.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Src Acts as an Effector for Ku70-dependent Suppression of Apoptosis through Phosphorylation of Ku70 at Tyr-530

Morii

Kubota

Honda

et al. 2017

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Edited by Xiao-Fan WangSrc-family tyrosine kinases are widely expressed in many cell types and participate in a variety of signal transduction pathways. Despite the significance of Src in suppression of apoptosis, its mechanism remains poorly understood. Here we show that Src acts as an effector for Ku70-dependent suppression of apoptosis. Inhibition of endogenous Src activity promotes UV-induced apoptosis, which is impaired by Ku70 knockdown. Src phosphorylates Ku70 at Tyr-530, being close to the possible acetylation sites involved in promotion of apoptosis. Src-mediated phosphorylation of Ku70 at Tyr-530 decreases acetylation of Ku70, whereas Src inhibition augments acetylation of Ku70. Importantly, knockdown-rescue experiments with stable Ku70 knockdown cells show that the nonphosphorylatable Y530F mutant of Ku70 reduces the ability of Ku70 to suppress apoptosis accompanied by augmentation of Ku70 acetylation. Our results reveal that Src plays a protective role against hyperactive apoptotic cell death by reducing apoptotic susceptibility through phosphorylation of Ku70 at Tyr-530.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Src Acts as an Effector for Ku70-dependent Suppression of Apoptosis through Phosphorylation of Ku70 at Tyr-530

Morii

Kubota

Honda

et al. 2017

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…20) Cell fractionation and Western blotting were performed as described previously. 16,20,21) Immunofluorescence Confocal images were obtained with a Fluoview FV500 confocal laser scanning microscope (Olympus, Tokyo, Japan), as described. 1) In brief, cells were fixed in 4% paraformaldehyde for 20 min at room temperature and permeabilized in phosphate-buffered saline (PBS) containing 0.1% saponin and 3% bovine serum albumin at room temperature.…”

Section: Highlighted Paper Selected By Editor-in-chiefmentioning

confidence: 99%

The Truncated Isoform of the Receptor Tyrosine Kinase ALK Generated by Alternative Transcription Initiation (ALK<sup>ATI</sup>) Induces Chromatin Structural Changes in the Nucleus in a Kinase Activity-Dependent Manner

Takakura

Yamaguchi

Honda

et al. 2017

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

Anaplastic lymphoma kinase (ALK) is a receptor-type tyrosine kinase that promotes cell growth upon stimulation with ligands such as midkine and pleiotrophin. Recently, a truncated isoform of ALK was identified in a variety of tumors. This isoform is expressed from a novel ALK transcript initiated from a de novo alternative transcription initiation (ATI) site in ALK intron 19 (referred to as ALK ATI ). ALK ATI , which consists of only the intracellular kinase domain, localizes to the nucleus as well as the cytoplasm. However, its nuclear role is unknown. In this study, we determined that ALK ATI promoted chromatin structural changes in the nucleus in a kinase activity-dependent manner. We found that expression of ALK ATI increased the level of the heterochromatin marker Lys9 tri-methylated histone H3. In addition, we demonstrated that ALK ATI phosphorylated the nuclear protein A-kinase anchoring protein 8 (AKAP8) and altered its subcellular localization from the insoluble fraction to the soluble fraction. These results suggest that ALK ATI induces chromatin structural changes and heterochromatinization through phosphorylation of AKAP8 in the nucleus.Key words anaplastic lymphoma kinase; nuclear tyrosine kinase; A-kinase anchoring protein 8; heterochromatinization; alternative transcription initiation; chromatin structural change Chromatin structure and organization are dynamically changed during cellular processes, such as proliferation, differentiation, DNA damage responses, and tumorigenesis.

show abstract

c‐Abl induces stabilization of histone deacetylase 1 (HDAC1) in a kinase activity‐dependent manner

Aoyama

Yamaguchi

Yuki

et al. 2015

Cell Biology International

Self Cite

View full text Add to dashboard Cite

c-Abl is a non-receptor-type tyrosine kinase that regulates various cellular events, including cell proliferation, differentiation, and apoptosis, through phosphorylation of cytoplasmic and nuclear targets. Although we showed that c-Abl induces histone deacetylation, the molecular mechanisms of this phenomenon are largely unknown. Here, we analyzed the effect of c-Abl on the expression of histone deacetylase 1 (HDAC1), because c-Abl was shown to be involved in maintenance of nuclear protein levels of HDAC1. Co-transfection of HDAC1 with c-Abl increased the levels of HDAC1 protein in a kinase activity-dependent manner without affecting its mRNA levels. Treatment with the proteasome inhibitor MG132 increased protein levels of HDAC1 in cells transfected with HDAC1 but not in cells co-transfected with HDAC1 and c-Abl. Among class I HDACs, knockdown of endogenous c-Abl preferentially suppressed endogenous protein levels of HDAC1, suggesting that c-Abl stabilizes HDAC1 protein by inhibiting its proteasomal degradation. Subcellular fractionation showed that the stabilization of HDAC1 by c-Abl occurred in the nucleus. Despite the fact that HDAC1 was phosphorylated by co-expression with c-Abl, stabilization of HDAC1 by c-Abl was not affected by mutations in its sites phosphorylated by c-Abl. Co-expression with HDAC1 and nuclear-targeted c-Abl did not affect HDAC1 stabilization. Therefore, these results suggest that c-Abl induces HDAC1 stabilization possibly through phosphorylation of a cytoplasmic target that is involved in proteasomal degradation of HDAC1.

show abstract

Formation of long and winding nuclear F-actin bundles by nuclear c-Abl tyrosine kinase

Cited by 21 publications

References 63 publications

Src Acts as an Effector for Ku70-dependent Suppression of Apoptosis through Phosphorylation of Ku70 at Tyr-530

Src Acts as an Effector for Ku70-dependent Suppression of Apoptosis through Phosphorylation of Ku70 at Tyr-530

The Truncated Isoform of the Receptor Tyrosine Kinase ALK Generated by Alternative Transcription Initiation (ALK<sup>ATI</sup>) Induces Chromatin Structural Changes in the Nucleus in a Kinase Activity-Dependent Manner

c‐Abl induces stabilization of histone deacetylase 1 (HDAC1) in a kinase activity‐dependent manner

Contact Info

Product

Resources

About