mTOR kinase and the regulatory subunit of protein kinase A (PRKAR1A) spatially and functionally interact during

Manos Mavrakis1, Jennifer Lippincott-Schwartz, Constantine A Stratakis

  • 1Cell Biology and Metabolism Branch, Section on Endocrinology and Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5430, USA.

Autophagy
|January 6, 2007
PubMed

Insights

The regulatory subunit RIalpha of PKA interacts with mTOR kinase, localizing to autophagosomes and influencing autophagy regulation. This suggests a role for the RIalpha-mTOR complex in autophagosome maturation.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The regulatory subunit 1-alpha (RIalpha) of protein kinase A (PKA) and mTOR kinase are key regulators of mammalian autophagy.
  • RIalpha has been observed to localize on late endosomes and autophagosomal membranes.

Purpose of the Study:

  • To investigate the subcellular distribution of mTOR in relation to RIalpha and LC3.
  • To explore the functional implications of the RIalpha-mTOR interaction in autophagy.

Main Methods:

  • Immunofluorescence microscopy to determine colocalization of RIalpha, mTOR, Rab7, and LC3.
  • Biochemical assays to assess mTOR phosphorylation and activity.

Main Results:

  • mTOR was found to colocalize with RIalpha, Rab7, and LC3 on cellular membranes.
  • RIalpha was confirmed to interact with mTOR, affecting its phosphorylation and activity.
  • These findings indicate that mTOR is present on autophagosomal membranes.

Conclusions:

  • The RIalpha-mTOR complex is positioned on autophagosomal membranes.
  • RIalpha's regulation of mTOR activity suggests a role in autophagosome maturation.

Related Concept Videos

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...
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...
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...
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...
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...