GIPC and GAIP form a complex with TrkA: a putative link between G protein and receptor tyrosine kinase pathways. Academic Article uri icon

Overview

abstract

  • NGF initiates the majority of its neurotrophic effects by promoting the activation of the tyrosine kinase receptor TrkA. Here we describe a novel interaction between TrkA and GIPC, a PDZ domain protein. GIPC binds to the juxtamembrane region of TrkA through its PDZ domain. The PDZ domain of GIPC also interacts with GAIP, an RGS (regulators of G protein signaling) protein. GIPC and GAIP are components of a G protein-coupled signaling complex thought to be involved in vesicular trafficking. In transfected HEK 293T cells GIPC, GAIP, and TrkA form a coprecipitable protein complex. Both TrkA and GAIP bind to the PDZ domain of GIPC, but their binding sites within the PDZ domain are different. The association of endogenous GIPC with the TrkA receptor was confirmed by coimmunoprecipitation in PC12 (615) cells stably expressing TrkA. By immunofluorescence GIPC colocalizes with phosphorylated TrkA receptors in retrograde transport vesicles located in the neurites and cell bodies of differentiated PC12 (615) cells. These results suggest that GIPC, like other PDZ domain proteins, serves to cluster transmembrane receptors with signaling molecules. When GIPC is overexpressed in PC12 (615) cells, NGF-induced phosphorylation of mitogen-activated protein (MAP) kinase (Erk1/2) decreases; however, there is no effect on phosphorylation of Akt, phospholipase C-gamma1, or Shc. The association of TrkA receptors with GIPC and GAIP plus the inhibition of MAP kinase by GIPC suggests that GIPC may provide a link between TrkA and G protein signaling pathways.

publication date

  • March 1, 2001

Research

keywords

  • Carrier Proteins
  • GTP-Binding Proteins
  • Neuropeptides
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA

Identity

PubMed Central ID

  • PMC30968

Scopus Document Identifier

  • 0035158872

Digital Object Identifier (DOI)

  • 10.1091/mbc.12.3.615

PubMed ID

  • 11251075

Additional Document Info

volume

  • 12

issue

  • 3