Related Experiment Video

Updated: Jul 12, 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

Stress-activated protein kinase-mediated down-regulation of the cell integrity pathway mitogen-activated protein

Marisa Madrid1, Andrés Núñez, Teresa Soto

  • 1Department of Genetics and Microbiology, Facultad de Biología, University of Murcia, 30071 Murcia, Spain.

Molecular Biology of the Cell
|September 1, 2007
PubMed

Insights

Stress-activated protein kinase (SAPK) pathway phosphatases Pyp1p, Pyp2p, and Ptc1p are crucial for deactivating the Pmk1p MAPK under osmotic stress in fission yeast. These phosphatases also regulate basal Pmk1p activity and cell cycle-dependent phosphorylation.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Biochemistry

Background:

  • Mitogen-activated protein kinase (MAPK) Pmk1p in fission yeast regulates cell integrity pathways, responding to various stresses.
  • Pmp1p is the sole known phosphatase for Pmk1p inactivation.
  • The stress-activated protein kinase (SAPK) pathway, involving Sty1p MAPK and Atf1p, is activated under stress conditions.

Purpose of the Study:

  • To investigate the role of the SAPK pathway and specific phosphatases in Pmk1p deactivation under hypertonic stress.
  • To identify phosphatases involved in regulating basal Pmk1p activity and its cell cycle-dependent phosphorylation.
  • To provide biochemical evidence for PP2C-type phosphatases acting on multiple MAPKs.

Main Methods:

  • Investigated Pmk1p deactivation under hypertonic stress using genetic and biochemical approaches.
  • Assessed the involvement of Sty1p, Atf1p, Pyp1p, Pyp2p, and Ptc1p in Pmk1p regulation.
  • Performed in vitro and in vivo association and dephosphorylation assays.
  • Analyzed Pmk1p phosphorylation patterns throughout the cell cycle.

Main Results:

  • The SAPK pathway, regulated by Atf1p, is essential for Pmk1p deactivation under hypertonic stress.
  • Tyrosine phosphatases Pyp1p and Pyp2p, and serine/threonine phosphatase Ptc1p, are involved in Pmk1p dephosphorylation during osmostress.
  • Pyp1p and Ptc1p, alongside Pmp1p, regulate basal Pmk1p activity and associate with Pmk1p.
  • Ptc1p is the first identified PP2C-type phosphatase acting on multiple MAPKs in yeast.
  • Pmk1p phosphorylation oscillates with the cell cycle, peaking at cell separation, with Pmp1p playing a key role.

Conclusions:

  • The SAPK pathway and specific phosphatases (Pyp1p, Pyp2p, Ptc1p) play critical roles in Pmk1p inactivation during osmotic stress.
  • Pyp1p and Ptc1p exhibit dual regulation of Pmk1p activity through both stress-dependent and basal mechanisms.
  • Pmk1p activity is tightly regulated throughout the cell cycle, particularly during cytokinesis, by phosphatases like Pmp1p.

More Related Videos

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation06:12

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation

Published on: May 3, 2024

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors10:17

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors

Published on: April 29, 2022

Related Concept Videos

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...
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...
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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...