Role for Tyrosine Phosphorylation of A-kinase Anchoring Protein 8 (AKAP8) in Its Dissociation from Chromatin and the Nuclear Matrix

Kubota, Sho; Morii, Mariko; Yuki, Ryuzaburo; Yamaguchi, Noritaka; Yamaguchi, Hiromi; Aoyama, Kazumasa; Kuga, Tetsurō; Tomonaga, Takeshi; Yamaguchi, Naoto

doi:10.1074/jbc.m115.643882

Cited by 23 publications

(36 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

“…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). Because we have learned from our own experiences that the inhibitory potency of Na 3 VO 4 , albeit an inorganic compound, against the activity of protein-tyrosine phosphatases is drastically lost (i) at neutral pH and (ii) by freeze-thawing, we dissolve Na 3 VO 4 in H 2 O just before use or store a Na 3 VO 4 stock solution in single-use aliquots at Ϫ20°C.…”

Section: Discussionmentioning

confidence: 99%

“…The nucleotides for shRNA were annealed and subcloned into the BglII-XbaI site of the pENTR4/H1 vector (provided by H. Miyoshi) (19, 70 -72). The EBNA1-based episomal pEBmulti/ neo/H1 vector, which encodes the H1 promoter and a neomycin-resistant gene, was generated from the pEBmulti/neo vector (Wako Pure Chemical Industries, Osaka, Japan) by replacing the CAG promoter with the H1 promoter as described (24,71). pEBmulti/neo/H1-sh(c-Src) was constructed as follows: the SpeI sites were created at the both ends of H1-sh(c-Src) by PCR with 5Ј-GTTGTCGACGGTACCAC-TAGTCATCAACCCGCTCCAAGGAATCGC-3Ј (sense) and 5Ј-TATACTAGTCGACGGTACCTGTTCGTTGCAACA-AATTGATAAGCAATGCT-3Ј (antisense), and the SpeI fragment of the PCR product was subcloned into the SpeI site of the pEBmulti/neo vector (24,71).…”

Section: Methodsmentioning

confidence: 99%

“…We have shown that Lyn, a Src member, is imported into and rapidly exported from the nucleus (21) and that nuclear tyrosine phosphorylation has a role in global changes of chromatin structure and histone modifications (13,(22)(23)(24). 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%

“…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%

See 4 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: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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

show abstract

A recognizable phenotype related to 19p13.12 microdeletion

Souza

Sgardioli

Vieira

2018

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Submicroscopic deletions in chromosome 19 have been rarely reported. We reported a male patient presenting with neurodevelopmental delay and facial dysmorphisms with a de novo 19p13.11p13.12 deletion of approximately 1.4 Mb. To date, there are seven cases with deletions overlapping the 19p13.11-p13.12 region described in the literature. A region of 800 kb for branchial arch defects in the proximal region of 19p13.12, and another minimal critical region of 305 kb for hypertrichosis, synophrys, and protruding front teeth have been proposed previously. We suggest that the shortest region of overlap could be refined to an approximately 53 kb region shared within all patients, encompassing part of BRD4 and AKAP8L genes and the AKAP8 gene. Based on the genotype-phenotype correlation of the present case and cases with overlapping deletions described in the literature, it was possible to recognize a consistent phenotype characterized by microcephaly, ear abnormalities, rounded face, synophrys, arched or upwardly angulated eyebrows, short nose, anteverted nares, prominent cheeks, teeth abnormalities, and developmental delay.

show abstract

Tyrosine Phosphorylation of the Pioneer Transcription Factor FoxA1 Promotes Activation of Estrogen Signaling

Yamaguchi¹,

Shibazaki²,

Yamada³

et al. 2016

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

The pioneer transcription factor FoxA1 plays an important role in estrogen signaling by opening closed chromatin and promoting recruitment of the estrogen receptor to its target regions in DNA. In this study, we analyzed tyrosine phosphorylation of FoxA1 by the non-receptor-type tyrosine kinase c-Abl. c-Abl was shown to phosphorylate FoxA1 at multiple sites, especially in the N- and C-terminal regions. Tyr429 and Tyr464 were identified as the major phosphorylation sites in the FoxA1 C-terminal region. The phosphomimetic and nonphosphorylatable FoxA1 mutants were generated by glutamic acid and phenylalanine substitutions at these tyrosine residues, respectively. The phosphomimetic FoxA1 promoted the activation of estrogen signaling, whereas the nonphosphorylatable FoxA1 suppressed its activation. Stimulation with the epidermal growth factor, which activates c-Abl, enhanced the activation of estrogen signaling. In contrast, the c-Abl inhibitor imatinib reduced its activation. The phosphomimetic FoxA1 mutant showed a higher affinity toward histone H3 than the wild-type. These results suggest that c-Abl-mediated phosphorylation of FoxA1 promotes the activation of estrogen signaling by inducing its binding to histones. J. Cell. Biochem. 118: 1453-1461, 2017. © 2016 Wiley Periodicals, Inc.

show abstract

Role for Tyrosine Phosphorylation of A-kinase Anchoring Protein 8 (AKAP8) in Its Dissociation from Chromatin and the Nuclear Matrix

Cited by 23 publications

References 59 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

A recognizable phenotype related to 19p13.12 microdeletion

Tyrosine Phosphorylation of the Pioneer Transcription Factor FoxA1 Promotes Activation of Estrogen Signaling

Contact Info

Product

Resources

About