Related Experiment Video

Updated: Aug 20, 2026

Development and Application of Rapamycin-regulated Tyrosine Phosphatases
06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

The Pim kinases control rapamycin-resistant T cell survival and activation

Casey J Fox1, Peter S Hammerman, Craig B Thompson

  • 1Abramson Family Cancer Research Institute and Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.

The Journal of Experimental Medicine
|January 12, 2005
PubMed

Insights

Mice lacking both Pim-1 and Pim-2 kinases show increased sensitivity to rapamycin, revealing these kinases regulate T cell survival and proliferation. This uncovers a rapamycin-insensitive pathway crucial for immune responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • The physiological roles of Pim-1 and Pim-2 kinases in immune responses are not fully understood.
  • Overexpression of Pim-1 or Pim-2 can contribute to lymphoid transformation.

Purpose of the Study:

  • To investigate the endogenous function of Pim-1 and Pim-2 kinases in T cells.
  • To elucidate the role of Pim kinases in regulating lymphocyte survival, growth, and proliferation in response to immunosuppressants like rapamycin.

Main Methods:

  • Generation and analysis of T cells from Pim-1(-/-)Pim-2(-/-) knockout mice.
  • Assessment of T cell sensitivity to rapamycin.
  • Evaluation of lymphocyte survival, growth, and proliferation.

Main Results:

  • T cells lacking both Pim-1 and Pim-2 kinases exhibit heightened sensitivity to rapamycin.
  • Pim-1 and Pim-2 promote rapamycin-resistant survival of lymphocytes.
  • Pim kinases regulate lymphocyte growth and proliferation, similar to the rapamycin target TOR.
  • Rapamycin completely suppresses the immune response of Pim-1(-/-)Pim-2(-/-) T cells, while having minimal effect on wild-type T cells.

Conclusions:

  • Endogenous levels of Pim-1 and Pim-2 kinases are essential for T cells to mount an immune response in the presence of rapamycin.
  • A rapamycin-insensitive pathway involving Pim kinases regulates T cell growth and survival.
  • Findings have implications for understanding rapamycin's immunomodulatory effects and developing new immunotherapeutics.

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

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...
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...
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...