Related Experiment Video

Updated: Jan 4, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

585

CD146 Regulates Growth Factor-Induced mTORC2 Activity Independent of the PI3K and mTORC1 Pathways

Wenyi Xu1, Huijuan Hua2, Yueh-Ho Chiu3

  • 1Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing 100193, China; College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.

Cell Reports
|October 31, 2019
PubMed

Insights

Growth factors activate mechanistic target of rapamycin complex 2 (mTORC2) signaling via CD146. This interaction stabilizes mTORC2, enhancing cell proliferation and survival by linking environmental cues to mTORC2 regulation.

Area of Science:

  • Cell Biology
  • Molecular Signaling
  • Biochemistry

Background:

  • Mechanistic target of rapamycin complex 2 (mTORC2) regulates critical cellular processes like proliferation, survival, and metabolism.
  • The precise mechanisms by which extracellular stimuli, such as growth factors (GFs), activate mTORC2 are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanism linking growth factor stimulation to mTORC2 activation in human endothelial cells.
  • To identify the role of transmembrane cell adhesion protein CD146 in mediating GF-induced mTORC2 signaling.

Main Methods:

  • Investigated the interaction between CD146 and mTORC2 components upon growth factor stimulation.
  • Utilized phosphorylation site analysis and protein-protein interaction studies.
  • Assessed the impact of CD146-Rictor complex formation on Rictor stability and mTORC2 activity.

Main Results:

  • Demonstrated that growth factor stimulation induces phosphorylation of the CD146 cytoplasmic tail.
  • Identified a direct interaction between the phosphorylated CD146 KKGK motif and Rictor, the key subunit of mTORC2.
  • Showed that CD146-Rictor complex formation protects Rictor from degradation, specifically upregulating mTORC2 activity without affecting PI3K or mTORC1 pathways.
  • Confirmed that CD146-mediated mTORC2 activation promotes endothelial cell proliferation and survival.

Conclusions:

  • Established CD146 as a crucial mediator of growth factor-induced mTORC2 activation in human endothelial cells.
  • Uncovered a novel mechanism where CD146 stabilizes mTORC2, thereby linking extracellular signals to cellular growth and survival.
  • Provided a molecular link between environmental cues and the regulation of mTORC2 activity.
Keywords:
CD146PI3KRictorcell proliferationmTORC1mTORC2signal transduction

More Related Videos

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

2.2K
A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

14.2K

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...
4.6K
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...
5.2K
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...
11.7K
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...
7.1K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
7.0K
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...
7.8K