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Related Concept Videos

Phosphorylation01:02

Phosphorylation

53.6K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
53.6K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

8.6K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
8.6K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

14.9K
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...
14.9K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

6.0K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
6.0K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

17.2K
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...
17.2K
Drug Metabolism: Phase I Reactions01:17

Drug Metabolism: Phase I Reactions

4.6K
A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
4.6K

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Related Experiment Video

Updated: Jan 13, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

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Cytochrome-P450 phosphorylation as a functional switch.

Barbara Oesch-Bartlomowicz1, Franz Oesch

  • 1Institute of Toxicology, University of Mainz, Obere Zahlbacher Strasse 67, Germany. Oeschb@mail.uni-mainz.de

Archives of Biochemistry and Biophysics
|December 5, 2002
PubMed
Summary
This summary is machine-generated.

Xenobiotic metabolizing cytochromes P450 (CYP) are rapidly inactivated by phosphorylation, controlled by Protein Kinase A (PKA). This phosphorylation acts as a switch, impacting drug metabolism and toxicity.

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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

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Oligopeptide Competition Assay for Phosphorylation Site Determination
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Oligopeptide Competition Assay for Phosphorylation Site Determination

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Related Experiment Videos

Last Updated: Jan 13, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
09:32

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

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Oligopeptide Competition Assay for Phosphorylation Site Determination
09:16

Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

8.8K

Area of Science:

  • Biochemistry
  • Pharmacology
  • Molecular Biology

Background:

  • Xenobiotic metabolizing cytochromes P450 (CYP) are crucial for drug metabolism.
  • CYP activity is regulated by various mechanisms, including enzyme induction and post-translational modifications.
  • Phosphorylation is a known post-translational modification affecting protein function.

Purpose of the Study:

  • To investigate the role and mechanism of CYP phosphorylation in regulating CYP activity.
  • To identify the specific kinases and motifs involved in CYP phosphorylation.
  • To understand the functional consequences of CYP phosphorylation on xenobiotic metabolism and drug effects.

Main Methods:

  • In vitro phosphorylation assays using purified protein kinases and CYPs.
  • Phosphorylation studies in intact cells (V79 cells, hepatocytes) and whole organisms (rats).
  • Site-directed mutagenesis to identify phosphorylation sites and their role in enzyme activity.

Main Results:

  • CYP phosphorylation is isoenzyme-selective, with Protein Kinase A (PKA) identified as a major catalyst.
  • The PKA recognition motif (Arg-Arg-X-Ser) is present in some CYPs, notably CYP2B1/2B2 and CYP2E1.
  • Phosphorylation of CYP2B1 leads to immediate catalytic inactivation, acting as a rapid switch, with Ser(138) identified as the key phosphorylation site.

Conclusions:

  • CYP phosphorylation by PKA is a rapid and selective mechanism for controlling CYP activity.
  • This phosphorylation switch significantly impacts the metabolism of genotoxic compounds and the efficacy/toxicity of cancer drugs.
  • Understanding CYP phosphorylation is vital for predicting drug metabolism, toxicity, and therapeutic outcomes.