MAPK and GPCRs Flashcards
How does Ras get activated and what does it do?
Ras is activated when it exchanges GDP for GTP. Once active, Ras can activate various downstream pathways like the PI3K/AKT pathway, RAF/MEK/ERK pathway, and TIAM1/RAC pathway.
What role does Tiam1 play in cell signalling?
Tiam1 is an exchange factor for Rac1. When Ras activates Tiam1, it leads to Rac1 exchanging GDP for GTP, making Rac1 active and promoting cell mobility.
How does Ras activate PI3K and what is the result?
Ras-GTP activates PI3K, which then phosphorylates PIP2 to form PIP3. PIP3 activates cytoplasmic kinases, including AKT, promoting cell survival.
What is the effect of AKT activation?
AKT promotes cell growth, inhibits apoptosis, and supports overall cell survival.
Describe the RAF/MEK/ERK pathway activation by Ras.
Ras-GTP activates RAF, which in turn activates MEK. MEK phosphorylates ERK, and ERK enters the nucleus to regulate genes that promote cell cycle progression and proliferation.
How do steroid hormones like estrogen act in cell signalling?
Steroid hormones like estrogen cross the plasma membrane (due to their hydrophobicity), bind to receptors, and the activated complex enters the nucleus to regulate gene transcription, promoting cell proliferation and survival.
What happens when Ras activates the TIAM1/RAC pathway?
Ras-GTP activates TIAM1, which in turn activates RAC. RAC regulates the cytoskeleton, influencing cell motility and shape, essential for migration and invasion.
What role does estrogen play in breast cancer?
In postmenopausal women, estrogen mainly circulates from adipose tissue and can contribute to breast cancer by interacting with receptors and promoting cell proliferation.
How is PI3K activated by RTKs?
RTKs activate PI3K by interacting with the SH2 domain of p85, a subunit of PI3K, which binds to phosphotyrosine residues on the RTK intracellular tail.
What is the role of adrenaline in GPCR signaling?
Adrenaline binds to a β-adrenergic GPCR, activating Gα, which stimulates adenylyl cyclase to produce cAMP. cAMP activates protein kinase A (PKA), leading to cellular responses like energy release.
What are G-protein-coupled receptors (GPCRs)?
GPCRs are a large family of cell surface receptors involved in numerous physiological processes, including smell, taste, and vision. They interact with heterotrimeric G proteins to relay signals.
How does the pituitary gland signal through GPCRs?
The pituitary gland releases TSH, which binds to a GPCR. This activates phospholipase C-β, generating IP3 and DAG, which release calcium and activate protein kinase C, regulating cell growth.
How is G-protein activation initiated?
A ligand binds to a GPCR, causing a shape change. This activates the G proteins by replacing GDP with GTP in the Gα subunit, leading to further signal propagation.
What is the role of IP3 and DAG in GPCR signalling?
IP3 stimulates calcium release from the smooth ER, while DAG stays in the membrane and activates protein kinase C, which regulates various cellular processes.
