Paracrine signalling and MAPK Flashcards
What is paracrine signalling?
Paracrine signalling involves molecules released by one cell acting on neighbouring target cells.
What is the role of Epidermal Growth Factor (EGF)?
EGF stimulates cell proliferation and is released from the salivary glands, pancreas, and duodenum.
How do ion-channel coupled receptors work?
Ligand binds to the receptor, causing it to open, allowing ions to flow into the cell. This is common in neurotransmission.
What are enzyme-coupled receptors? Give an example.
Enzyme-coupled receptors are membrane receptors that, when activated, trigger intracellular enzymatic activity. An example is receptor tyrosine kinases (RTKs).
What are the three main types of cell surface receptors?
Ion-channel coupled receptors
Enzyme-coupled receptors
G-protein coupled receptors
What do RTKs bind to, and what do they promote?
RTKs bind to growth factors (proteins/peptides) that promote cell growth, survival, motility, and proliferation.
What happens when there is overexpression of EGFR (HER1/ErbB1)?
Overexpression of EGFR can lead to uncontrolled cell division, contributing to cancers like basal and squamous cell carcinomas.
What are the three domains of RTKs?
N-terminal domain (extracellular)
Transmembrane domain
Intracellular tyrosine kinase domain
How does phosphorylation affect proteins?
Protein kinases attach a phosphate group (from ATP) to specific amino acids (Ser, Thr, Tyr), activating proteins. Protein phosphatases remove these phosphates to deactivate proteins.
What does EGFR activation trigger in the MAPK pathway?
EGFR activation leads to receptor dimerization and phosphorylation of tyrosine residues, starting a cascade that activates the MAPK pathway.
What is the role of RAS in the MAPK pathway?
RAS is a small GTPase that, when activated by SOS, exchanges GDP for GTP, triggering a MAPK signalling cascade that affects cell proliferation and survival.
What are the key transcription factors activated by ERK in the MAPK pathway?
Transcription factors such as c-Myc, Fos, and Jun, which promote cell proliferation, survival, and migration.
How do protein kinases contribute to cancer?
Mutations or overexpression of protein kinases, like EGFR, can lead to continuous signaling and unchecked cell division, contributing to cancer.
What mutations are commonly seen in cancer cells?
50% of carcinomas show EGFR overexpression, leading to excessive cell division.
90% of pancreatic cancers have a Ras point mutation that causes prolonged activation.
What mutation is commonly seen in melanomas?
Over 60% of melanomas have a Raf mutation (RafV600E), which is resistant to some drug therapies.
What is the impact of the Ras mutation in pancreatic cancer?
A point mutation (G → T, Gly → Val) in Ras leads to prolonged activation because Ras cannot hydrolyze GTP properly, leading to continuous MAPK pathway signalling.
What is the significance of mutant Ras in cancer?
Mutant Ras is one of the most potent oncogenes, often leading to sustained activation of downstream signaling pathways that drive cancer progression.
