RTKs II Flashcards
What is Ras?
A small GTPase activated by RTK phosphorylation via Grb2 and Sos
What does activated Ras initiate?
MAP kinase pathway, resulting in gene transcription
How are MAP kinase modules organised
Scaffold proteins
What small GTPases regulate the actin cytoskeleton?
Rho, Rac, Cdc42
What is the role of PI 3-kinase
Convert PIP2 into PIP3.
What is PIP3
Membrane bound second messenger that is recognised by PH (Pleckstrin homology) domains
What is PTEN?
A phosphatase that converts PIP3 to PIP2. It is the most frequently disrupted tumour suppressor in cancer
What is an important role of PIP3
Akt activation which promotes cell survival and growth
What does PLC-gamma do?
Cleaves PIP2 to produce the second messengers DAG and IP3
What downregulates RTK?
Desphosphorylation, endocytosis and degredation (ubiquitylation - Cdl)
What activates intracellular signalling networks?
EGF
What does Erk do?
Change in protein activity or gene expression
What is special about the structure of Ras?
A 20kDa protein containing a switch helix that interacts with Raf and can change shape
What happens when Erk translocates into the nucleus?
Phosphorylates TCF, which binds SRE and starts transcription of c-fos gene
Is ras activation long or short lived?
Short
How are RTKs inactivated?
By phosphatases
How is Ras inactivated?
By specific GAPS
What are two proto-oncogenes in this pathway?
Ras and B-Raf
Which kinase participates in many negative feedback loops
Erk
What do phosphoinositides acts as?
Signal transducers
What phosphorylates and activates Akt?
mTOR and PDK1
What does Akt do?
Phosphorylates and activates Bad (an apoptosis inhibitory protein) -inhibits apoptosis
