Molecular Cell Biology: Cell Signalling and Phosphorylation

This set covers vocabulary related to molecular cell signaling, focusing on phosphorylation-dependent docking sites, protein binding domains, and experimental mutations used to study signaling pathways.

SH2 domain

A compact “plug-in” module that recognizes phospho-tyrosines and a particular amino acid side chain in the neighboring area without disturbing the protein’s folding or function.

PTB domain

A Phosphotyrosine-binding domain; an example includes the domain from Dok1, which complexes to a $pY$ peptide corresponding to the RTK called RET.

RTK (Receptor Tyrosine Kinase)

A type of enzyme-coupled receptor that, when activated, becomes a signaling hub through autophosphorylation, generating high-affinity docking sites for signaling proteins.

PI3K (Phosphoinositide 3-kinase)

An enzyme structurally distant from protein kinases that catalyzes the phosphorylation of phosphoinositides, such as converting $PI(4,5)P_2$ to $PI(3,4,5)P_3$.

$$PI(3,4,5)P_3$$

Phosphatidylinositol 3,4,5-trisphosphate; a phospholipid that acts as a signaling-dependent docking site at the plasma membrane for proteins containing a PH domain.

PH domain (Pleckstrin Homology)

A protein domain that binds to the phospholipid $PI(3,4,5)P_3$, allowing proteins like PDK1 and Akt to dock at the plasma membrane.

EGFP (Enhanced Green Fluorescent Protein)

A fluorescent protein often used in live-cell imaging with a peak excitation wavelength of $488\,nm$ and a peak emission wavelength of $507\,nm$.

Phospho-mimetic substitution

An experimental tool where amino acids like Aspartate (Asp/D) or Glutamate (Glu/E) are used to mimic the negative charge of a phosphate group to test if phosphorylation is sufficient for a physiological outcome.

Non-phosphorylatable substitution

An experimental tool where amino acids such as Alanine (Ala/A) or Valine (Val/V) replace Serine (Ser/S) or Threonine (Thr/T) to prove if phosphorylation at a specific site is required for a signaling event.

SH3 domain

A protein domain that recognizes and binds to proline-rich motifs.

Akt

A protein kinase in the PI3K signaling pathway that, when activated by PDK1 and mTOR, phosphorylates Bad to inhibit apoptosis.

Bad

A pro-apoptotic protein that, when phosphorylated, is inactivated by binding to 14-3-3 protein, thereby promoting cell survival.

14-3-3 protein

A signaling protein that binds to phosphorylated Bad, keeping it sequestered and inactive in the cytosol to inhibit apoptosis.

PDK1

Phosphoinositide-dependent protein kinase 1; it contains a PH domain and is involved in the activation of Akt at the plasma membrane.