Rap2 function requires palmitoylation and recycling endosome localization

Biochem Biophys Res Commun. 2009 Jan 23;378(4):732-7. doi: 10.1016/j.bbrc.2008.11.107. Epub 2008 Dec 4.

Abstract

Rap2A, Rap2B, and Rap2C are Ras-like small G proteins. The role of their post-translational processing has not been investigated due to the lack of information on their downstream signaling. We have recently identified the Traf2- and Nck-interacting kinase (TNIK), a member of the STE20 group of mitogen-activated protein kinase kinase kinase kinases, as a specific Rap2 effector. Here we report that, in HEK293T cells, Rap2A (farnesylated) and Rap2C (likely farnesylated), but not Rap2B (geranylgeranylated), require palmitoylation for membrane-association and TNIK activation, whereas all Rap2 proteins, including Rap2B, require palmitoylation for induction of TNIK-mediated phenotype, the suppression of cell spreading. Furthermore, we report for the first time that, in COS-1 cells, Rap2 proteins localize, and recruit TNIK, to the recycling endosomes, but not the Golgi nor the endoplasmic reticulum, in a palmitoylation-dependent manner. These observations implicate the involvement of palmitoylation and recycling endosome localization in cellular functions of Rap2 proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • Endoplasmic Reticulum / enzymology
  • Endosomes / enzymology*
  • Enzyme Activation
  • Germinal Center Kinases
  • Golgi Apparatus / enzymology
  • Humans
  • Lipoylation*
  • Molecular Sequence Data
  • Phenotype
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / metabolism
  • rap GTP-Binding Proteins / metabolism*
  • ras Proteins / metabolism*

Substances

  • Germinal Center Kinases
  • Protein Serine-Threonine Kinases
  • TNIK protein, human
  • RAP2A protein, human
  • RAP2B protein, human
  • Rap2C protein, human
  • rap GTP-Binding Proteins
  • ras Proteins