Receptors and cell signalling Flashcards
Describe endocrine signalling
long distance signalling;
diffuse through blood;
long-lasting (takes minutes to reach target cell sometimes)
Paracrine signalling
acts locally upon (short lived) e.g. neurotransmitters
Autocrine signalling
all cells with receptor (including itself) respond to the ligand (growth factors of cancer cells)
juxtacrine/direct
to attached cell
acetylcholine effects on heart, skeletal muscle, and salivary gland:
heart cells relax, skeletal muscles contract, salivary gland secrete saliva
Describe a Guanine exchange factor
receptors on GCPR change a GDP for a GTP on G proteins
What is PLC? What is it’s function?
phospholipase C cleaves PIP2 into IP3 and DAG
What does Gs protein do?
cAMP pathway
How does the Cholera toxin modify the G protein
I keeps Ga in the GTP active form indefinitely by adding a ribose (to G protein);
Cl secretion is constantly turned on
another term for turning up a signal
potentiate
another term for turning down a signal
attenuate
another term for turning down a signal
attenuate
What desensitizes a signal?
hormone levels drop;
phosphodiesterases remove cAMP;
receptors are sequestrated (endosome) and destroyed (endosome to lysosome via proteases);
GRK (GCPR kinase) phosphorylate the receptor so that arrestin can bind to it
What are the different G proteins and what does each do?
Gaq-PLC, DAG, Ca, PKC
Gai-cAMP inhibition
Gas-cAMP
Ga12-RhoGEFs
What receptor is associated with epinephrine?
beta andren…ic
What receptor is associated with histamine?
histamine receptor
What receptor is associated with epinephrine and norepinephrine?
alpha andrenergic receptor
What receptor is associated with dopamine?
Dopamine receptor
What receptor is associated with light?
Rhodopsin
What is a calcium mediated pathway?
Gqa GCPR
Describe the Gqa pathway cascade
ligand binds, GDP->GTP, G with GTP activates PLC, PLC separates PIP2 into DAG and IP3, IP3 binds to Ca channel on ER/SR,
Ca and DAG activate PKC, Ca forms calmodulin complex
What is needed to activate PKC?
DAG and Ca
What makes an acceptable nuclear hormone signal molecule?
hydrophobic molecules are best (steroid hormones), NO, growth factors
How does an intracellular receptor work?
There is a DNA binding domain on a receptor, once ligand binds then an inhibitory protein is released from the receptor and acts like a transcription factor
What are some hydrophobic ligands that are nuclear hormone signals?
cortisol, estradol, testosterone, vitamin D3, thyroxine, and retinoic acid
If a CpG island is hypermethalated then what is occuring?
promoter region is inaccessible, DNA transcription does not occur
How does hypermethylation of miRNA coding regions of DNA result in cancer?
miRNA binds complementary to mRNA to silence genes. If this is not occuring then bad RNA cannot be silenced through that mechanism
If the epigenetic is Highly altered what might that indicate?
cancers have their own specific epigenetic patterns, as well as histone modifications
If the CpG islands have a lot of methylation on their histones then what does that indicate?
There is likely transcription of this area
What is an easier modification: to methylate histone or DNA?
histone
What are the two hits that have to occur in order to get cancer?
DNA repair pathways must be mutated
Oncogenes must be expressed
place in order of lowest to highest penetrance? Transposon, cell signalling, or DNA repair gene mutations?
Transposon lowest
cell signalling
DNA repair highest
What are some mitogen pathway proteins? What do they do?
src, erb, and ras
If up-regulated they promote cell proliferation
What are Growth inhibitor pathway proteins?
rb and apc
