Mutations and cell signalling Flashcards
What is the meadiator family receptor that have a physical link between the intracellular cytoskeleton and the ECM
Integrin
What are the 3 types of Integrin signalling
- ITAM-mediated signalling
- ITAM-independent signalling
- Combined signalling
What does integrin signalling do to the cell?
Helps in cell migation/adhesion and ECM assembly
Integrin signalling: inside-out the cell, describe 4 points (not a short answer)
- Initiation—> chemitaxins activate GCPRs
- this actiavtion causes activateion of PKC—>activated PKD—->ACTIVATES RAP/GTPase
- These molecules propagate SIGNALS TO THE INTEGRINS, altering conformation and increasing affinity to extracellular ligands
- 2 short intracellular complexes transmit structural changes to the integrin heads, allowing more effective binding
Integrin signalling: outside-in the cell
- Once integrin activated and higher affinity for ligands, causesproteins in the ECM to bind. triggering outside in signalling
- This binding of integrins to their ligands conveys both mechanincal and chemical signals across the mem. this signals are important for processes like cell migration, proliferation, and survival
- the binding of ligands to the extracellular domain of integrins lead to conformational changes that are transmitted to the intracellular domain. This results in the assembly of signaling complexes within the cell, which can activate various downstream signaling pathways
What is leucocyte adhesion deficiency type 1?
Autosomal recessive disorder of immune system
characterised by recurrent bacterial infections that are life threatening
Caused by impaired extravastion of monocytes
Due to absence of or mutaions in integrin-2
Lack of or failure to activate or cluster is likely the source of LAD-1
Whats the action of activin?
- Growth and dev
- Embryonic stem cell maintenece and diff
- Ovarian and testicular dev and function
- Immune system
What is the action of inhibin?
Block activin action
What is the fucntion of myostatin?
Muscle and adipocyte development and differentiation
What is the main fucntion of CSK in Src?
Phosphorylates Src only just without excessive activation, so preventing cancer.
What does Src pathways do? (3)
- motility
- Proliferation and survival
- cell-cell adhesion
How can Srccause cancer? give the example of when one of the 3 main functions stops,
Motility and cell proliferation carries on like normal, however if cell-cell adhesion stops this gives a hallmark to metastsing cancer cell as the cell is dividing rapidly and can move to anywhere because there is no cell adhesion meaning they can spread!! VERY BAD UNCONTROLLABLE DIVISIONWHEN SRC IS ACTIVATED EXCESSIVELY
What is the difference between c and v src?
c-Src has a tail that has a phosphorylation where it will allow itself to bind to its own SH2 and block its activity.
vsrc has lost its tail meaning closure of the src is not possible meaning it is more active than the c-src,there are also mutations is SH3 domain which does not allow that domain to interact with itsself??
Tyrosine to be phosphorylated further faster and therefore 3 diff things,
1. prevention of ligands, 2. prevention of binding to SH2 domain, 3. activation of the catalyctic region.
Why is Src an oncogene?
Unregulated Src activity leads to unregulated cellular proliferation, increaced and motility.
What is the function of CREB IN TRANSCRPTION OF GENES ETC.?
Transcriptional coactivator–> can help TFs to active genes.(acts as a scaffolding—>brings various TFs TO THE TRANSCRIPTION MACHINERY)
Histone Acetyltransferase- add acetyl groups to histone proteins, making the DNA more accessible for transcription.
