Mitotic phosphotyrosine network analysis reveals that tyrosine phosphorylation regulates Polo-like kinase 1 (PLK1)

Caron, D, Byrne, DP, Thebault, P, Soulet, D, Landry, CR, Eyers, PA ORCID: 0000-0002-9220-2966 and Elowe, S
(2016) Mitotic phosphotyrosine network analysis reveals that tyrosine phosphorylation regulates Polo-like kinase 1 (PLK1). SCIENCE SIGNALING, 9 (458). rs14-.

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Tyrosine phosphorylation is closely associated with cell proliferation. During the cell cycle, serine and threonine phosphorylation plays the leading role, and such phosphorylation events are most dynamic during the mitotic phase of the cell cycle. However, mitotic phosphotyrosine is not well characterized. Although a few functionally-relevant mitotic phosphotyrosine sites have been characterized, evidence suggests that this modification may be more prevalent than previously appreciated. Here, we examined tyrosine phosphorylation in mitotic human cells including those on spindle-associated proteins.? Database mining confirmed ~2000 mitotic phosphotyrosine sites, and network analysis revealed a number of subnetworks that were enriched in tyrosine-phosphorylated proteins, including components of the kinetochore or spindle and SRC family kinases. We identified Polo-like kinase 1 (PLK1), a major signaling hub in the spindle subnetwork, as phosphorylated at the conserved Tyr217 in the kinase domain. Substitution of Tyr217 with a phosphomimetic residue eliminated PLK1 activity in vitro and in cells. Further analysis showed that Tyr217 phosphorylation reduced the phosphorylation of Thr210 in the activation loop, a phosphorylation event necessary for PLK1 activity. Our data indicate that mitotic tyrosine phosphorylation regulated a key serine/threonine kinase hub in mitotic cells and suggested that spatially separating tyrosine phosphorylation events can reveal previously unrecognized regulatory events and complexes associated with specific structures of the cell cycle.

Item Type: Article
Uncontrolled Keywords: Cell Line, Humans, Tyrosine, Cell Cycle Proteins, Proto-Oncogene Proteins, Mitosis, Phosphorylation, Spindle Apparatus, Protein Domains, Protein Serine-Threonine Kinases, Polo-Like Kinase 1
Depositing User: Symplectic Admin
Date Deposited: 27 Jan 2017 09:34
Last Modified: 02 Jan 2024 09:54
DOI: 10.1126/scisignal.aah3525
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