Related Experiment Video

Updated: Jun 11, 2026

Phospho Flow Cytometry with Fluorescent Cell Barcoding for Single Cell Signaling Analysis and Biomarker Discovery
08:38

Phospho Flow Cytometry with Fluorescent Cell Barcoding for Single Cell Signaling Analysis and Biomarker Discovery

Published on: October 4, 2018

CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling

J Irie-Sasaki1, T Sasaki, W Matsumoto

  • 1Amgen Institute, Department of Medical Biophysics, University of Toronto, Ontario, Canada.

Nature
|February 24, 2001
PubMed

Insights

The protein tyrosine phosphatase CD45 suppresses Janus kinase (JAK) activity, revealing a new role in regulating cytokine receptor signaling. This finding impacts understanding of immune cell function and development.

Area of Science:

  • Immunology
  • Cell Signaling
  • Molecular Biology

Background:

  • Protein tyrosine phosphatases (PTPases) and protein tyrosine kinases regulate cell signaling.
  • CD45, a transmembrane PTPase, is crucial for T and B cell antigen receptor signaling.
  • CD45 targets Src-family kinases, but its broad expression suggests additional roles.

Purpose of the Study:

  • To investigate the function of CD45 beyond antigen receptor signaling.
  • To determine if CD45 regulates cytokine receptor signaling pathways.
  • To identify novel substrates and functions of CD45 in hematopoietic cells.

Main Methods:

  • Gene targeting to disrupt the cd45 gene in mice.
  • In vitro biochemical assays to assess CD45-JAK interactions.
  • Analysis of JAK/STAT pathway activation and cellular responses (proliferation, hematopoiesis, antiviral activity).

Main Results:

  • CD45 suppresses Janus kinase (JAK) activity and negatively regulates cytokine receptor signaling.
  • Disruption of cd45 enhances JAK and STAT protein activation by cytokine and interferon receptors.
  • CD45 directly dephosphorylates and binds to JAK kinases in vitro.
  • CD45 negatively regulates interleukin-3-mediated proliferation, erythropoietin-dependent hematopoiesis, and antiviral responses.

Conclusions:

  • CD45 functions as a hematopoietic JAK phosphatase.
  • CD45 negatively regulates cytokine receptor signaling pathways.
  • This identifies a novel role for CD45 in modulating immune responses and hematopoiesis.

More Related Videos

Time-resolved Förster Resonance Energy Transfer Assays for Measurement of Endogenous Phosphorylated STAT Proteins in Human Cells07:12

Time-resolved Förster Resonance Energy Transfer Assays for Measurement of Endogenous Phosphorylated STAT Proteins in Human Cells

Published on: September 9, 2021

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

Cell-surface Signaling01:21

Cell-surface Signaling

Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Cell Signaling Feedback Loops01:07

Cell Signaling Feedback Loops

Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
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...
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...