Gene interactions and pathways from curated databases and text-mining
Mol Cell 2002, PMID: 11804587

Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1.

Parrini, Maria Carla; Lei, Ming; Harrison, Stephen C; Mayer, Bruce J

Pak1, a serine/threonine kinase that regulates the actin cytoskeleton, is an effector of the Rho family GTPases Cdc42 and Rac1. The crystal structure of Pak1 revealed an autoinhibited dimer that must dissociate upon GTPase binding. We show that Pak1 forms homodimers in vivo and that its dimerization is regulated by the intracellular level of GTP-Cdc42 or GTP-Rac1. The dimerized Pak1 adopts a trans-inhibited conformation: the N-terminal inhibitory portion of one Pak1 molecule in the dimer binds and inhibits the catalytic domain of the other. One GTPase interaction can result in activation of both partners. Another ligand, betaPIX, can stably associate with dimerized Pak1. Dimerization does not facilitate Pak1 trans-phosphorylation. We conclude that the functional significance of dimerization is to allow trans-inhibition.

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Text Mining Data

GTP-Cdc42 — Pak1: " We show that Pak1 forms homodimers in vivo and that its dimerization is regulated by the intracellular level of GTP-Cdc42 or GTP-Rac1 "

Pak1 — GTP-Rac1: " We show that Pak1 forms homodimers in vivo and that its dimerization is regulated by the intracellular level of GTP-Cdc42 or GTP-Rac1 "

Manually curated Databases

  • IRef Biogrid Interaction: PAK1 — PAK1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PAK1 — PAK1 (colocalization, biochemical)
  • IRef Biogrid Interaction: PAK1 — PAK1 (direct interaction, enzymatic study)
  • IRef Hprd Interaction: PAK1 — PAK1 (in vivo)
  • IRef Hprd Interaction: PAK1 — PAK1 (in vitro)
  • NCI Pathway Database CDC42 signaling events: CDC42/GTP complex (CDC42) → PAK1 (PAK1) (modification, activates)
    Evidence: assay, physical interaction
  • NCI Pathway Database CDC42 signaling events: CDC42/GTP complex (CDC42) → PAK1 (dimer) complex (PAK1) (modification, activates)
    Evidence: assay, physical interaction
  • NCI Pathway Database CDC42 signaling events: PAK1 (PAK1) → PAK1 (dimer) complex (PAK1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database RAC1 signaling pathway: RAC1/GTP complex (RAC1) → PAK1 (PAK1) (modification, activates)
    Evidence: mutant phenotype
  • NCI Pathway Database RAC1 signaling pathway: RAC1/GTP complex (RAC1) → PAK1 (dimer) complex (PAK1) (modification, activates)
    Evidence: mutant phenotype
  • NCI Pathway Database RAC1 signaling pathway: PAK1 (PAK1) → PAK1 (dimer) complex (PAK1) (modification, collaborate)
    Evidence: mutant phenotype
  • Reactome Reaction: RAC1 → RAC1 (reaction)
  • Reactome Reaction: VAV1 → PAK3 (indirect_complex)
  • Reactome Reaction: SOS1 → LAT (reaction)
  • Reactome Reaction: PAK3 → RAC1 (indirect_complex)
  • Reactome Reaction: GRB2 → GRB2 (reaction)
  • Reactome Reaction: VAV1 → RAC1 (reaction)
  • Reactome Reaction: PAK1 → VAV2 (reaction)
  • Reactome Reaction: GRB2 → PAK2 (reaction)
  • Reactome Reaction: PLCG2 → RAC1 (reaction)
  • Reactome Reaction: PAK2 → PAK2 (reaction)
  • Reactome Reaction: PAK2 → VAV3 (reaction)
  • Reactome Reaction: SHC1 → SHC1 (reaction)
  • Reactome Reaction: VAV1 → LAT (reaction)
  • Reactome Reaction: LAT → SHC1 (reaction)
  • Reactome Reaction: VAV3 → VAV3 (reaction)
  • Reactome Reaction: LAT → LAT (reaction)
  • Reactome Reaction: LCP2 → PAK1 (reaction)
  • Reactome Reaction: LCP2 → VAV3 (reaction)
  • Reactome Reaction: GRAP2 → VAV3 (reaction)
  • Reactome Reaction: SOS1 → VAV1 (reaction)
  • Reactome Reaction: LCP2 → LAT (reaction)
  • Reactome Reaction: GRAP2 → LCP2 (reaction)
  • Reactome Reaction: GRAP2 → VAV2 (reaction)
  • Reactome Reaction: VAV2 → LAT (reaction)
  • Reactome Reaction: LCP2 → LCP2 (reaction)
  • Reactome Reaction: PAK2 → SOS1 (reaction)
  • Reactome Reaction: PAK2 → RAC1 (reaction)
  • Reactome Reaction: PAK2 → SHC1 (reaction)
  • Reactome Reaction: GRAP2 → PLCG2 (reaction)
  • Reactome Reaction: VAV1 → VAV1 (reaction)
  • Reactome Reaction: PAK2 → VAV2 (reaction)
  • Reactome Reaction: PLCG2 → LAT (reaction)
  • Reactome Reaction: PLCG1 → VAV1 (reaction)
  • Reactome Reaction: GRAP2 → VAV1 (reaction)
  • Reactome Reaction: GRB2 → RAC1 (reaction)
  • Reactome Reaction: PLCG1 → SHC1 (reaction)
  • Reactome Reaction: PAK1 → VAV1 (indirect_complex)
  • Reactome Reaction: PAK1 → PLCG1 (reaction)
  • Reactome Reaction: PAK3 → VAV3 (reaction)
  • Reactome Reaction: GRB2 → PLCG1 (reaction)
  • Reactome Reaction: LCP2 → RAC1 (reaction)
  • Reactome Reaction: GRB2 → VAV2 (reaction)
  • Reactome Reaction: PAK1 → LAT (reaction)
  • Reactome Reaction: PAK2 → VAV1 (reaction)
  • Reactome Reaction: PAK3 → RAC1 (reaction)
  • Reactome Reaction: LCP2 → SOS1 (reaction)
  • Reactome Reaction: PAK2 → VAV3 (indirect_complex)
  • Reactome Reaction: LCP2 → PLCG2 (reaction)
  • Reactome Reaction: PAK1 → RAC1 (indirect_complex)
  • Reactome Reaction: PAK1 → CDC42 (reaction)
  • Reactome Reaction: PAK2 → RAC1 (indirect_complex)
  • Reactome Reaction: LCP2 → VAV1 (reaction)
  • Reactome Reaction: PAK1 → SHC1 (reaction)
  • Reactome Reaction: SOS1 → VAV2 (reaction)
  • Reactome Reaction: PLCG1 → PLCG1 (reaction)
  • Reactome Reaction: PLCG1 → SOS1 (reaction)
  • Reactome Reaction: GRB2 → VAV1 (reaction)
  • Reactome Reaction: VAV1 → SHC1 (reaction)
  • Reactome Reaction: PLCG1 → LAT (reaction)
  • Reactome Reaction: VAV2 → RAC1 (reaction)
  • Reactome Reaction: SOS1 → VAV3 (reaction)
  • Reactome Reaction: PAK1 → PLCG2 (reaction)
  • Reactome Reaction: VAV2 → SHC1 (reaction)
  • Reactome Reaction: VAV1 → PAK3 (reaction)
  • Reactome Reaction: PAK2 → PLCG1 (reaction)
  • Reactome Reaction: GRB2 → LCP2 (reaction)
  • Reactome Reaction: PAK3 → VAV3 (indirect_complex)
  • Reactome Reaction: GRB2 → PLCG2 (reaction)
  • Reactome Reaction: VAV2 → VAV3 (reaction)
  • Reactome Reaction: LCP2 → SHC1 (reaction)
  • Reactome Reaction: GRAP2 → LAT (reaction)
  • Reactome Reaction: VAV2 → VAV2 (reaction)
  • Reactome Reaction: GRB2 → GRAP2 (reaction)
  • Reactome Reaction: PAK2 → LAT (reaction)
  • Reactome Reaction: SOS1 → SHC1 (reaction)
  • Reactome Reaction: VAV2 → VAV1 (reaction)
  • Reactome Reaction: RAC1 → VAV3 (reaction)
  • Reactome Reaction: GRB2 → LAT (reaction)
  • Reactome Reaction: PAK2 → PLCG2 (reaction)
  • Reactome Reaction: VAV1 → VAV3 (reaction)
  • Reactome Reaction: LCP2 → PLCG1 (reaction)
  • Reactome Reaction: PAK1 → VAV3 (reaction)
  • Reactome Reaction: LAT → RAC1 (reaction)
  • Reactome Reaction: PLCG2 → VAV3 (reaction)
  • Reactome Reaction: PLCG2 → VAV1 (reaction)
  • Reactome Reaction: GRB2 → SOS1 (reaction)
  • Reactome Reaction: VAV2 → PAK3 (reaction)
  • Reactome Reaction: PLCG2 → VAV2 (reaction)
  • Reactome Reaction: PLCG1 → RAC1 (reaction)
  • Reactome Reaction: GRB2 → VAV3 (reaction)
  • Reactome Reaction: GRB2 → PAK1 (reaction)
  • Reactome Reaction: LCP2 → PAK2 (reaction)
  • Reactome Reaction: PAK1 → PAK1 (reaction)
  • Reactome Reaction: PAK2 → VAV1 (indirect_complex)
  • Reactome Reaction: GRAP2 → PAK2 (reaction)
  • Reactome Reaction: PLCG2 → PLCG2 (reaction)
  • Reactome Reaction: PAK1 → SOS1 (reaction)
  • Reactome Reaction: GRAP2 → PAK1 (reaction)
  • Reactome Reaction: GRB2 → SHC1 (reaction)
  • Reactome Reaction: PAK1 → PAK2 (reaction)
  • Reactome Reaction: GRAP2 → PLCG1 (reaction)
  • Reactome Reaction: PAK1 → VAV3 (indirect_complex)
  • Reactome Reaction: GRAP2 → GRAP2 (reaction)
  • Reactome Reaction: SOS1 → RAC1 (reaction)
  • Reactome Reaction: PLCG2 → SOS1 (reaction)
  • Reactome Reaction: PAK2 → VAV2 (indirect_complex)
  • Reactome Reaction: PLCG1 → PLCG2 (reaction)
  • Reactome Reaction: GRAP2 → SOS1 (reaction)
  • Reactome Reaction: VAV2 → PAK3 (indirect_complex)
  • Reactome Reaction: SOS1 → SOS1 (reaction)
  • Reactome Reaction: GRAP2 → RAC1 (reaction)
  • Reactome Reaction: SHC1 → VAV3 (reaction)
  • Reactome Reaction: PLCG1 → VAV3 (reaction)
  • Reactome Reaction: PAK1 → RAC1 (reaction)
  • Reactome Reaction: SHC1 → RAC1 (reaction)
  • Reactome Reaction: PLCG1 → VAV2 (reaction)
  • Reactome Reaction: GRAP2 → SHC1 (reaction)
  • Reactome Reaction: PAK1 → VAV2 (indirect_complex)
  • Reactome Reaction: LCP2 → VAV2 (reaction)
  • Reactome Reaction: LAT → VAV3 (reaction)
  • Reactome Reaction: PAK1 → VAV1 (reaction)
  • Reactome Reaction: PLCG2 → SHC1 (reaction)
In total, 110 gene pairs are associated to this article in curated databases