Complex Signalling pathways Flashcards

1
Q

Binding positions of Rhodspin like, Secretin Like and Glutamate like

A
  • Smaller molecules bind in the cleft of TM segments
  • larger molecules often bind to th N-terminus or ECL
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2
Q

GTPase activity

A

GTPase activity of the alpha subunit is increased when bound to effector proteins

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3
Q

G protein selectivity

A

Certain receptors are more likely to bind to other G- proteins due to complementary recognition sequences

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4
Q

RHO system

A

Rho is a monomeric G protein activated by alpha subunits of the 12/13 subclass. Activated 12/13 subunits bind to GEFS, GEFS then bind RHO promoting guanonucleotide exchange. RHO then binds ROCK which inhibits myosin light chain phosphatase activity, PROMOTING CONTRACTILITY.

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5
Q

Termination of signalling

A
  1. Degradation or removal of agonists
  2. Receptor desensitisation/internalisation
  3. GTPase activity
  4. Degradation of second messengers
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6
Q

Heterologous desensitization

A

Non-specific and mediated by pKa and pKc. Serine and threonine residues in the intracellular loops and N-terminus are phosphoylated which makes G-Protein coupling less likely.

Residues to be phosphorylated are located in the THIRD INTRACELLULAR LOOP

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7
Q

Homologous Desensitization

A

GRK’s phosphorylate specific threonine and serine residues located in the C-terminal tail. Phosphorylation primes the receptor for B-arrestin binding. B-arrestin the recruits endocytotic mediatiors, Clathrin and Clathrin Adaptor Protein.

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8
Q

Post-endocytosis Outcomes

A
  • Enternalized proteins are either dephosphorylated and returned to the plasma membrane or degraded via a lysosoma or 26S proteasome pathway
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9
Q

Signal Maintenance of internalized receptors

A

The signal is generated at the plasma membrane and continues signalling in early endosomes through formation of RAS–RAF–MEK–ERK (RAS–RAF–MAPK/ERK kinase (also known as MAPKK)–extracellular signal-regulated kinase) complexes bound to the growth factor receptor-bound 2 (GRB2) adaptor for RTKs or β-arrestin for GPCRs. Activated ERK is released from the endosome and translocates to the nucleus to phosphorylate its targets. c

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10
Q

Roles of B-arrestin

A
  • Promotes degredation of 2nd messengers by recruiting phosphodiesterases and DAG kinase to the signalling site
  • Directly recruits and promotes a second wave of B-arrestin dependent, G protein independent signalling
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11
Q

pKa sequence

A

Arg-Arg-X-Ser/Thr

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