RRC ID 72507
Author Morii M, Kubota S, Hasegawa C, Takeda Y, Kometani S, Enomoto K, Suzuki T, Yanase S, Sato R, Akatsu A, Hirata K, Honda T, Kuga T, Tomonaga T, Nakayama Y, Yamaguchi N, Yamaguchi N.
Title Src-mediated tyrosine phosphorylation of PRC1 and kinastrin/SKAP on the mitotic spindle.
Journal Sci Rep
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.
Volume 11(1)
Pages 2616
Published 2021-1-28
DOI 10.1038/s41598-021-82189-1
PII 10.1038/s41598-021-82189-1
PMID 33510346
PMC PMC7844303
MeSH Cell Cycle Cell Cycle Proteins / metabolism* Centrosome / enzymology* HeLa Cells Humans Microtubule-Associated Proteins / metabolism* Phosphorylation Proto-Oncogene Proteins c-fyn / metabolism* Spindle Apparatus / enzymology*
IF 3.998
DNA material pcDNA/TO/myc-PRC1_wt (RDB19641) pcDNA/TO/myc-PRC1_Y464F (RDB19642) pcDNA/TO/myc-PRC1_Y464E (RDB19643) pcDNA/TO/myc-kinastrin_wt (RDB19644) pcDNA/TO/myc-kinastrin_Y87F (RDB19645) pcDNA/TO/myc-kinastrin_Y87E (RDB19646)