Src-mediated tyrosine phosphorylation of PRC1 and kinastrin/SKAP on the mitotic spindle

Abstract Src-family tyrosine kinases (SFKs) play important roles in a number of signal transduction events during mitosis, such as spindle formation. A relationship has been reported between SFKs and the mitotic spindle; however, the underlying mechanisms remain unclear. We herein demonstrated that...

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Autores principales: Mariko Morii, Sho Kubota, Chizu Hasegawa, Yumi Takeda, Shiori Kometani, Kyoko Enomoto, Takayuki Suzuki, Sayuri Yanase, Rika Sato, Aki Akatsu, Kensuke Hirata, Takuya Honda, Takahisa Kuga, Takeshi Tomonaga, Yuji Nakayama, Noritaka Yamaguchi, Naoto Yamaguchi
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:582649b7251e4fec9cadd5ac8cfb9f402021-12-02T13:24:17ZSrc-mediated tyrosine phosphorylation of PRC1 and kinastrin/SKAP on the mitotic spindle10.1038/s41598-021-82189-12045-2322https://doaj.org/article/582649b7251e4fec9cadd5ac8cfb9f402021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82189-1https://doaj.org/toc/2045-2322Abstract Src-family tyrosine kinases (SFKs) play important roles in a number of signal transduction events during mitosis, such as spindle formation. A relationship has been reported between SFKs and the mitotic spindle; however, the underlying mechanisms remain unclear. We herein demonstrated that SFKs accumulated in the centrosome region at the onset of mitosis. Centrosomal Fyn increased in the G2 phase in a microtubule polymerization-dependent manner. A mass spectrometry analysis using mitotic spindle preparations was performed to identify tyrosine-phosphorylated substrates. Protein regulator of cytokinesis 1 (PRC1) and kinastrin/small kinetochore-associated protein (kinastrin/SKAP) were identified as SFK substrates. SFKs mainly phosphorylated PRC1 at Tyr-464 and kinastrin at Tyr-87. Although wild-type PRC1 is associated with microtubules, phosphomimetic PRC1 impaired the ability to bind microtubules. Phosphomimetic kinastrin at Tyr-87 also impaired binding with microtubules. Collectively, these results suggest that tyrosine phosphorylation of PRC1 and kinastrin plays a role in their delocalization from microtubules during mitosis.Mariko MoriiSho KubotaChizu HasegawaYumi TakedaShiori KometaniKyoko EnomotoTakayuki SuzukiSayuri YanaseRika SatoAki AkatsuKensuke HirataTakuya HondaTakahisa KugaTakeshi TomonagaYuji NakayamaNoritaka YamaguchiNaoto YamaguchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mariko Morii
Sho Kubota
Chizu Hasegawa
Yumi Takeda
Shiori Kometani
Kyoko Enomoto
Takayuki Suzuki
Sayuri Yanase
Rika Sato
Aki Akatsu
Kensuke Hirata
Takuya Honda
Takahisa Kuga
Takeshi Tomonaga
Yuji Nakayama
Noritaka Yamaguchi
Naoto Yamaguchi
Src-mediated tyrosine phosphorylation of PRC1 and kinastrin/SKAP on the mitotic spindle
description Abstract Src-family tyrosine kinases (SFKs) play important roles in a number of signal transduction events during mitosis, such as spindle formation. A relationship has been reported between SFKs and the mitotic spindle; however, the underlying mechanisms remain unclear. We herein demonstrated that SFKs accumulated in the centrosome region at the onset of mitosis. Centrosomal Fyn increased in the G2 phase in a microtubule polymerization-dependent manner. A mass spectrometry analysis using mitotic spindle preparations was performed to identify tyrosine-phosphorylated substrates. Protein regulator of cytokinesis 1 (PRC1) and kinastrin/small kinetochore-associated protein (kinastrin/SKAP) were identified as SFK substrates. SFKs mainly phosphorylated PRC1 at Tyr-464 and kinastrin at Tyr-87. Although wild-type PRC1 is associated with microtubules, phosphomimetic PRC1 impaired the ability to bind microtubules. Phosphomimetic kinastrin at Tyr-87 also impaired binding with microtubules. Collectively, these results suggest that tyrosine phosphorylation of PRC1 and kinastrin plays a role in their delocalization from microtubules during mitosis.
format article
author Mariko Morii
Sho Kubota
Chizu Hasegawa
Yumi Takeda
Shiori Kometani
Kyoko Enomoto
Takayuki Suzuki
Sayuri Yanase
Rika Sato
Aki Akatsu
Kensuke Hirata
Takuya Honda
Takahisa Kuga
Takeshi Tomonaga
Yuji Nakayama
Noritaka Yamaguchi
Naoto Yamaguchi
author_facet Mariko Morii
Sho Kubota
Chizu Hasegawa
Yumi Takeda
Shiori Kometani
Kyoko Enomoto
Takayuki Suzuki
Sayuri Yanase
Rika Sato
Aki Akatsu
Kensuke Hirata
Takuya Honda
Takahisa Kuga
Takeshi Tomonaga
Yuji Nakayama
Noritaka Yamaguchi
Naoto Yamaguchi
author_sort Mariko Morii
title Src-mediated tyrosine phosphorylation of PRC1 and kinastrin/SKAP on the mitotic spindle
title_short Src-mediated tyrosine phosphorylation of PRC1 and kinastrin/SKAP on the mitotic spindle
title_full Src-mediated tyrosine phosphorylation of PRC1 and kinastrin/SKAP on the mitotic spindle
title_fullStr Src-mediated tyrosine phosphorylation of PRC1 and kinastrin/SKAP on the mitotic spindle
title_full_unstemmed Src-mediated tyrosine phosphorylation of PRC1 and kinastrin/SKAP on the mitotic spindle
title_sort src-mediated tyrosine phosphorylation of prc1 and kinastrin/skap on the mitotic spindle
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/582649b7251e4fec9cadd5ac8cfb9f40
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