The kelch repeat protein, Tea1, is a potential substrate target of the p21-activated kinase, Shk1, in the fission yeast, Schizosaccharomyces pombe

Hye Won Kim, Peirong Yang, Paola Catanuto, Fulvia Verde, Hong Lai, Hongyan Du, Fred Chang, Stevan Marcus

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

The p21-activated kinase (PAK) homolog, Shk1, is a critical component of a multifunctional Ras/Cdc42/PAK complex required for viability, polarized growth and cell shape, and sexual differentiation in the fission yeast, Schizosaccharomyces pombe. Substrate targets of the Shk1 kinase have not previously been described. Here we show that the S. pombe cell polarity factor, Tea1, is directly phosphorylated by Shk1 in vitro. We demonstrate further that Tea1 is phosphorylated in S. pombe cells and that its level of phosphorylation is significantly reduced in cells defective in Shk1 function. Consistent with a role for Tea1 as a potential downstream effector of Shk1, we show that a tea1 null mutation rescues the Shk1 hyperactivity-induced lethal phenotype caused by loss of function of the essential Shk1 inhibitor, Skb15. All phenotypes associated with Skb15 loss, including defects in actin cytoskeletal organization, chromosome segregation, and cytokinesis, are suppressed by tea1Δ, suggesting that Tea1 is a potential mediator of multiple Shk1 functions. S. pombe cells carrying a weak hypomorphic allele of shk1 together with a tea1Δ mutation exhibit a cytokinesis defective phenotype that is significantly more severe than that observed in the respective single mutants, providing evidence that Shk1 and Tea1 cooperate to regulate cytokinesis. In addition, we show that S. pombe cells carrying the orb2-34 allele of shk1 exhibit a pattern of monopolar growth similar to that observed in tea1Δ cells, suggesting that Shk1 and Tea1 may regulate one or more common processes involved in the regulation of polarized cell growth. Taken together, our results strongly implicate Tea1 as a potential substrate-effector of the Shk1 kinase.

Original languageEnglish (US)
Pages (from-to)30074-30082
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number32
DOIs
StatePublished - Aug 8 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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