Related Experiment Video

Updated: Aug 10, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Phosphoinositide breakdown and evidence for protein kinase C involvement during human NK killing

S C Chow1, J NG, C Nordstedt

  • 1Department of Immunology, Karolinska Institute, Stockholm, Sweden.

Cellular Immunology
|June 1, 1988
PubMed

Insights

Natural killer (NK) cell conjugation with target cells triggers inositol lipid breakdown in effector cells, requiring extracellular calcium. This process involves protein kinase C (PKC) activation, crucial for NK cell-mediated cytotoxicity.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Natural killer (NK) cells are crucial for innate immunity, eliminating infected or cancerous cells.
  • The precise molecular mechanisms underlying NK cell-mediated cytotoxicity are complex and still under investigation.
  • NK cell activation involves cell-cell interactions and signaling cascades within the effector cell.

Purpose of the Study:

  • To investigate the role of inositol lipid metabolism and protein kinase C (PKC) activation in human NK cell-mediated killing.
  • To determine the signaling events occurring in NK cells during conjugation with susceptible and resistant target cells.

Main Methods:

  • NK cell conjugation assays with K562 and Jurkat target cells.
  • Measurement of inositol lipid breakdown in NK cells.
  • Assessment of extracellular calcium requirement for NK cell activation.
  • Evaluation of the effects of sphingosine, phorbol esters (TPA, PDBU, 4-alpha-PDIDE), and diacylglycerol derivatives (OAG) on NK cell killing.
  • Analysis of PKC activation in human lymphocytes.

Main Results:

  • Conjugation with susceptible target cells (K562, Jurkat) induced inositol lipid breakdown in NK cells, unlike conjugation with resistant cells.
  • Extracellular calcium (Ca2+) was essential for this NK cell activation.
  • Sphingosine inhibited NK cell killing, while phorbol esters (TPA, PDBU) enhanced it at low concentrations.
  • The diacylglycerol derivative OAG increased NK cell killing and activated PKC in human lymphocytes.

Conclusions:

  • Phosphoinositide breakdown and subsequent protein kinase C (PKC) activation are strongly implicated in the mechanism of human NK cell-mediated killing.
  • These findings elucidate key intracellular signaling pathways involved in NK cell effector functions.

More Related Videos

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies09:54

Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies

Published on: May 22, 2020

Related Concept Videos

Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
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...
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...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...