Rho-Kinase Phosphorylates PAR-3 and Disrupts PAR Complex Formation

Masanori Nakayama, Takaaki M. Goto, Masayuki Sugimoto, Takashi Nishimura, Takafumi Shinagawa, Sigeo Ohno, Mutsuki Amano, Kozo Kaibuchi

Research output: Contribution to journalArticlepeer-review

110 Citations (Scopus)

Abstract

A polarity complex of PAR-3, PAR-6, and atypical protein kinase C (aPKC) functions in various cell polarization events. PAR-3 directly interacts with Tiam1/Taim2 (STEF), Rac1-specific guanine nucleotide exchange factors, and forms a complex with aPKC-PAR-6-Cdc42•GTP, leading to Rac1 activation. RhoA antagonizes Rac1 in certain types of cells. However, the relationship between RhoA and the PAR complex remains elusive. We found here that Rho-kinase/ROCK/ROK, the effector of RhoA, phosphorylated PAR-3 at Thr833 and thereby disrupted its interaction with aPKC and PAR-6, but not with Tiam2. Phosphorylated PAR-3 was observed in the leading edge, and in central and rear portions of migrating cells having front-rear polarity. Knockdown of PAR-3 by small interfering RNA (siRNA) impaired cell migration, front-rear polarization, and PAR-3-mediated Rac1 activation, which were recovered with siRNA-resistant PAR-3, but not with the phospho-mimic PAR-3 mutant. We propose that RhoA/Rho-kinase inhibits PAR complex formation through PAR-3 phosphorylation, resulting in Rac1 inactivation.

Original languageEnglish
Pages (from-to)205-215
Number of pages11
JournalDevelopmental Cell
Volume14
Issue number2
DOIs
Publication statusPublished - 12-02-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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