Related Experiment Videos

Rin1 is a negative regulator of the IL3 receptor signal transduction pathways

C M Hunker1, A Galvis, M L Veisaga

  • 1Department of Biological Sciences, Florida International University, University Park, Miami, Florida 33199, USA.

Anticancer Research
|April 20, 2006
PubMed

Insights

Rin1 protein selectively blocks IL-3 and BCR/ABL oncogene signaling, inhibiting cell proliferation. Depleting Rin1 promotes cell growth, revealing its crucial role in leukemia.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Cytokines bind cell-surface receptors, regulating cell growth and apoptosis.
  • Rin1 protein modulates Epidermal Growth Factor Receptor (EGFR) signaling and endocytosis.

Purpose of the Study:

  • To investigate the function of Rin1 in Interleukin-3 (IL-3) receptor signaling pathways.
  • To determine Rin1's role in BCR/ABL-induced cell proliferation.

Main Methods:

  • Retroviral expression of Rin1 and deletion mutants in cells.
  • RNA interference (RNAi) for Rin1 depletion.
  • Assessing activation of signaling pathways (Ras-Erk1/2, PI3K/Akt, JNK, p38K) and DNA synthesis.

Main Results:

  • Overexpression of Rin1 selectively inhibited IL-3-induced activation of Ras-Erk1/2 and PI3K/Akt pathways and DNA incorporation.
  • Rin1 depletion via RNAi led to increased cell growth.
  • Rin1 is essential for BCR/ABL-induced proliferation, and its expression blocked BCR/ABL-induced Erk1/2 activation.

Conclusions:

  • Rin1 plays a critical and selective role in IL-3 and BCR/ABL-mediated cell proliferation.
  • Rin1 has a novel function in leukemic cells, acting as a key regulator of oncogenic signaling pathways.

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...