Activation of c-Src and Fyn kinases by protein-tyrosine phosphatase RPTPalpha is substrate-specific and compatible

Related Experiment Video

Updated: Jun 28, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

Nathalie Vacaresse1, Bente Møller, E Michael Danielsen

  • 1Biotech Research and Innovation Center, Copenhagen Biocenter, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.

The Journal of Biological Chemistry
|October 25, 2008
PubMed

Insights

Protein tyrosine phosphatases like RPTPalpha regulate Src family kinases (SFKs) by directing substrate specificity and controlling activation. This reveals specific roles for phosphatases in SFK signaling networks.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Biochemistry

Background:

  • Src family kinases (SFKs) are crucial in numerous signaling pathways.
  • Regulation and substrate specificity of SFKs are key questions in cell signaling.
  • Protein-tyrosine phosphatases (PTPs), including RPTPalpha and SHP2, modulate SFK activity.

Purpose of the Study:

  • To investigate how RPTPalpha influences the substrate specificity and regulation of c-Src and Fyn.
  • To understand the role of RPTPalpha in response to epidermal growth factor (EGF) and platelet-derived growth factor (PDGF).

Main Methods:

  • Studied the effects of RPTPalpha on c-Src and Fyn activity.
  • Investigated substrate specificity using specific SFK substrates like Paxillin and Cbp/PAG.
  • Analyzed the localization of RPTPalpha within lipid rafts.
  • Examined the recruitment of Csk kinase in response to RPTPalpha activity.

Main Results:

  • RPTPalpha directs SFK specificity toward substrates like Paxillin and Cbp/PAG in a growth factor-dependent manner.
  • RPTPalpha is found in lipid rafts, where it regulates Fyn and Cbp/PAG.
  • Growth factor-induced SFK activation in lipid rafts requires RPTPalpha.
  • RPTPalpha-mediated phosphorylation of Paxillin and Cbp/PAG triggers Csk recruitment, indicating negative feedback.

Conclusions:

  • RPTPalpha plays a specific role in dictating SFK substrate specificity.
  • RPTPalpha is essential for growth factor-mediated SFK activation within lipid rafts.
  • Individual SFK-controlling PTPs have distinct roles in SFK regulation and substrate selection.

More Related Videos

Development and Application of Rapamycin-regulated Tyrosine Phosphatases06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Oligopeptide Competition Assay for Phosphorylation Site Determination09:16

Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

Related Concept Videos

Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...