L03 - Cell Signalling and Cancer Test Questions
& 100% Correct Answers Latest Update
Describe the process of receptor tyrosine kinase dimerisation and activation... - ✔✔-binding of
the signalling molecule induces receptor dimerisation (activates internal tyrosine kinase domain_
-this enables kinase domains of neighbouring receptors to cross-phosphorylate each other on
multiple tyrosine residues (autophosphorylation)
-phosphorylation of tyrosine residues creates high affinity docking sites for a variety of proteins (for
down stream signalling): >Grb-2 (MAP kinase pathway) >PI 3-kinase (PI 3-kinase pathway)
What does RAS activation act as? - ✔✔as a switch - key intermediate in the MAP kinase pathway
What type of gene is the activation of RAS? - ✔✔oncogene - activating RAS mutations are found
in around 30% of human tumours
What is RAS a master regulator of? - ✔✔many signalling pathways - does a lot of things in a cell which
makes targeting for cancer a lot harder
How is RAS - G-protein activates and inactivated - ✔✔RAS-GTP in the active form - GEF
(guanine nucleotide exchange factor ) stimulates the exchange of GDP for GTP
RAS-GDP is the inactive form - GAP (GTPase activating protein - yet it does deactivate) stimulates
intrinsic GTPase activity and hydrolysis of GTP
, Describe the MAPK pathway... - ✔✔-RAS binds to RAF family members and promotes RAF-
dimerisation and activation in a complex multi-faceted process involving phosphorylation (indirect
as RAS isn't putting the phosphate of RAF)
-activation of RAF kinase leads to rapid signalling through the MAPK cascade (RAF -> MEK -> ERK) via a
series of activating phosphorylation events
-phospho-ERK translocates to the nucleus and activates transcription factors such as FOS and JUN by
phosphorylation - this leads to changes in gene expression profiles
What does PI3K pathway stand for? - ✔✔phosphatidylinositol 3 kinase pathway
Describe the PI3K pathway... - ✔✔-the enzyme PI 3-kinase is activated by binding to
phosphorylated Tyr residues on RTKs
-PI 3-kinase catalyses the phosphorylation of PI(4,5)P2 to generate PI(3,4,5)P3
-PI(3,4,5)P3 acts as a docking site for 2 proteins, PDK1 and AKT
-upon binding PDK1 phosphorylates and activates AKT
-active AKT is released into the cytosol for downstream signalling (can activate mTOR, cause gene
transcription and cell cycle progression or phosphorylate and sequester pro-apoptotic proteins)
Describe the process from PI yo PI(3,4,5)P3... - ✔✔-PI - the inositol head group gets phosphorylated
-this forms PI(4,5)P2 (a substrate for PI3 kinase
-P1(4,5)P2 is phosphorylated by PI3K to produce PI(3,4,5)P3
What is PI(3,4,5)P3? - ✔✔a second messenger
What is a second messenger? - ✔✔a small molecule that passes signal on within the cell
How is EGFR family signalling switched off? - ✔✔1. remove extracellular signal so no stimulation
2. switching off activated receptor tyrosine kinase by protein tyrosine phosphatases (PTPs) -
remove phosphate group internally
3. dephosphorylation of target proteins by serine/threonine phosphatases
4. PTEN (phosphatase and tennis homolog deleted on chromosome 10) removal of PI(3,4,5)P3 signal
& 100% Correct Answers Latest Update
Describe the process of receptor tyrosine kinase dimerisation and activation... - ✔✔-binding of
the signalling molecule induces receptor dimerisation (activates internal tyrosine kinase domain_
-this enables kinase domains of neighbouring receptors to cross-phosphorylate each other on
multiple tyrosine residues (autophosphorylation)
-phosphorylation of tyrosine residues creates high affinity docking sites for a variety of proteins (for
down stream signalling): >Grb-2 (MAP kinase pathway) >PI 3-kinase (PI 3-kinase pathway)
What does RAS activation act as? - ✔✔as a switch - key intermediate in the MAP kinase pathway
What type of gene is the activation of RAS? - ✔✔oncogene - activating RAS mutations are found
in around 30% of human tumours
What is RAS a master regulator of? - ✔✔many signalling pathways - does a lot of things in a cell which
makes targeting for cancer a lot harder
How is RAS - G-protein activates and inactivated - ✔✔RAS-GTP in the active form - GEF
(guanine nucleotide exchange factor ) stimulates the exchange of GDP for GTP
RAS-GDP is the inactive form - GAP (GTPase activating protein - yet it does deactivate) stimulates
intrinsic GTPase activity and hydrolysis of GTP
, Describe the MAPK pathway... - ✔✔-RAS binds to RAF family members and promotes RAF-
dimerisation and activation in a complex multi-faceted process involving phosphorylation (indirect
as RAS isn't putting the phosphate of RAF)
-activation of RAF kinase leads to rapid signalling through the MAPK cascade (RAF -> MEK -> ERK) via a
series of activating phosphorylation events
-phospho-ERK translocates to the nucleus and activates transcription factors such as FOS and JUN by
phosphorylation - this leads to changes in gene expression profiles
What does PI3K pathway stand for? - ✔✔phosphatidylinositol 3 kinase pathway
Describe the PI3K pathway... - ✔✔-the enzyme PI 3-kinase is activated by binding to
phosphorylated Tyr residues on RTKs
-PI 3-kinase catalyses the phosphorylation of PI(4,5)P2 to generate PI(3,4,5)P3
-PI(3,4,5)P3 acts as a docking site for 2 proteins, PDK1 and AKT
-upon binding PDK1 phosphorylates and activates AKT
-active AKT is released into the cytosol for downstream signalling (can activate mTOR, cause gene
transcription and cell cycle progression or phosphorylate and sequester pro-apoptotic proteins)
Describe the process from PI yo PI(3,4,5)P3... - ✔✔-PI - the inositol head group gets phosphorylated
-this forms PI(4,5)P2 (a substrate for PI3 kinase
-P1(4,5)P2 is phosphorylated by PI3K to produce PI(3,4,5)P3
What is PI(3,4,5)P3? - ✔✔a second messenger
What is a second messenger? - ✔✔a small molecule that passes signal on within the cell
How is EGFR family signalling switched off? - ✔✔1. remove extracellular signal so no stimulation
2. switching off activated receptor tyrosine kinase by protein tyrosine phosphatases (PTPs) -
remove phosphate group internally
3. dephosphorylation of target proteins by serine/threonine phosphatases
4. PTEN (phosphatase and tennis homolog deleted on chromosome 10) removal of PI(3,4,5)P3 signal
