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Related Concept Videos

Phosphorylation01:02

Phosphorylation

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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...
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Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

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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...
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PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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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...
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Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

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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...
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Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

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Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

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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.
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Updated: Sep 15, 2025

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

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Phosphorylation-Inducing Molecules for Regulating Dynamic Cellular Processes.

Rajaiah Pergu1, Vedagopuram Sreekanth1,2,3, Praveen Kokkonda1

  • 1Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States.

Journal of the American Chemical Society
|July 14, 2025
PubMed
Summary
This summary is machine-generated.

A new platform using phosphorylation-inducing chimeric small molecules (PHICS) enables controlled protein phosphorylation. This advance allows precise regulation of cellular processes like cancer signaling and neuronal function without harsh conditions.

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Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Biochemistry

Background:

  • Protein phosphorylation is crucial for cellular communication.
  • Existing phosphorylation-inducing chimeric small molecules (PHICS) have limitations, including dependence on serum starvation and target overexpression.
  • Previous PHICS showed limited control over AMP-activated protein kinase (AMPK) recruitment and activity.

Purpose of the Study:

  • To develop a novel AMPK PHICS platform for controlled protein phosphorylation under physiological conditions.
  • To overcome the limitations of previous PHICS technology.
  • To demonstrate the platform's utility in regulating key cellular processes.

Main Methods:

  • Development of an advanced AMPK PHICS platform.
  • Application of PHICS to control oncogenic signaling pathways.
  • Utilizing PHICS to modulate protein phase separation in neurons.

Main Results:

  • The new AMPK PHICS platform operates effectively without serum starvation.
  • It enables dose- and temporally-controlled phosphorylation of target proteins.
  • PHICS successfully inhibited oncogenic Bruton's tyrosine kinase (BTK) in cancer cells and controlled Liprin-α3 phase separation in neurons.

Conclusions:

  • The developed AMPK PHICS platform offers precise control over protein phosphorylation.
  • This technology can be applied to diverse cellular processes, including cancer and neuroscience.
  • The platform holds significant potential for basic research and biomedical applications.