Biology And Biomedical Sciences BIOL 2960 Lecture Notes - Lecture 12: Adenylyl Cyclase, Glycogen Phosphorylase, Protein Kinase
13 Dec 2016
School
Department
15 February 2016
Lectures 12: STP’s and Enzymes
I. Signal Transduction Pathways (STP’s)
A. Signaling Cascades
1. In class exercise (order of epinephrine GPCR): epinephrine, receptor, Gs-GTP,
Adenylyl cyclase, cAMP, PKA, phosphor kinase, glycogen phosphorylase, glucose
B. Growth Factor Signaling Pathway
1. Cells don’t divide on their own, they divide in response to signals from other cells
a. We don’t want rogue cells dividing on their own → causes cancer
b. Growth factor proteins bind to receptors on cells to divide
2. Protein tyrosine kinase receptor
a. Growth factor binds → dimerizes the receptor → intracellular components with
protein kinase activates → transphosphorylation of intracellular domains of
receptor (each domain phosphorylates the neighboring domain) → provides
docking site for proteins → stimulates “sos” which acts like a GPCR to stimulate
the exchange of GDP for GTP on G-protein → results in activated Ras g-protein
→ (activates a phosphorylation cascade of 3 protein kinases) activates Raf →
activates MEK → activates MAPK → phosphorylates other effectors
b. This will ultimately result in changes in nuclear transcription factors to alter gene
expression for division
3. Ras G-protein is a key player in this STP
a. Ras G-protein has intrinsic GTPase activity which is important in the regulation
of its activation and inactivation
b. A genetic change in the normal Ras “proto-oncogene” leads to a point mutation
substitution changing one AA (AA 12, glycine into valine) which will destroy the
intrinsic GTPase activity of Ras
• This mutation makes the Ras gene an oncogene (cancer causing)
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