Related Experiment Video

Updated: Jun 24, 2026

Study of Protein-protein Interactions in Autophagy Research
14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

Kinome signaling through regulated protein-protein interactions in normal and cancer cells

Tony Pawson1, Michael Kofler

  • 1Samuel Lunenfeld Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada. pawson@lunenfeld.ca

Current Opinion in Cell Biology
|March 21, 2009
PubMed

Insights

Protein kinases use linked domains to control molecular information flow in cell signaling. These interactions regulate kinase activity and substrate recognition in both normal and cancer pathways.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Signaling

Background:

  • Molecular information flow in cellular signaling relies on protein phosphorylation by kinases.
  • Kinase and interaction domains mediate these processes, particularly in cytoplasmic tyrosine kinases like Src and Abl.
  • Intramolecular interactions between these domains influence kinase activity and substrate binding.

Purpose of the Study:

  • To elucidate the interplay between catalytic and interaction domains in protein kinases.
  • To understand how intramolecular interactions affect kinase function and signaling pathways.
  • To explore the evolution of complex signaling properties through domain linkage.

Main Methods:

  • Analysis of cytoplasmic tyrosine kinases (Src, Abl, Fes, ZAP-70).
  • Investigation of intramolecular interactions between kinase and SH2 domains.
  • Examination of effects on substrate recognition and kinase activity.

Main Results:

  • Kinase and SH2 domains exhibit intrinsic phosphorylation and binding properties.
  • Intramolecular interactions between linked domains vary by protein.
  • These interactions modulate substrate recognition and catalytic activity.
  • Mechanisms linking catalytic activity stimulation to substrate recognition were identified.

Conclusions:

  • Protein kinases evolve complex signaling properties via stepwise domain linkage.
  • Interplay of catalytic and interaction domains is crucial for normal and oncogenic signaling.
  • Understanding these mechanisms offers insights into signaling pathway regulation.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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...