Allosteric Regulation by Protein Phosphorylation

Allosteric Regulation by Protein Phosphorylation

1. Major mechanism by which cells response to extracelluar stimuli

   • e.g. hormones, light, neutrophic factors, cytokines
   • Virtually every kind of neuronal protein is regulated by phosphorylation

2. Protein Kinase transfers phosphate groups from ATP to side chains of serine, threonine or tyrosine on the substrate protein.

   • How is the activity of the substrate protein terminated?
     • By protein phosphatase = dephosphorylates by hydrolysis
   • Protein Kinases may also activate or modify other protein kinases downstream, or transcription factors such as ERK
   • There are 2 kinds of Protein Kinases
     • 99% phosphorylate serine or threonine residues
       • e.g. cAMP-dependant PKA which when activated translocates to nucleus to phosphorylate CREB on residue ser133.
     • 1% phosphorylate tyrosine kinases (PTK)
       • e.g. growth-factor receptors where ligand binding induces dimerisation and the Tyr residues are transphosphorylated