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RTKs

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imissyou419's version from 2016-12-17 04:37

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Question Answer
When inactivated, most RTKs are ____, insulin receptors are _____most RTKs are monomers (ligand binding causes dimerization), insulin receptors are dimers (ligand binding causes conformational changes bringing 2 kinase domains together)
What are the 2 types of ligands RTKs are activated by?cell surface bound ligand, secreted growth factor; allowing for highly specific signalling
Give an example of cell surface bound receptorsephrin - allows for bidirectional signalling (signalling downstream of ligand and downstream of receptor)
What does ephrin signalling regulate?angiogenesis, axon guidance, synaptic plasticity
Dimeric ligand, example and actionPDGF is a covalently linked dimer with 2 distinct receptor binding domain, it can crosslink and dimerize 2 adjacent PDGF receptors to initiate signalling (autophosphorylation)
Monomeric ligands, example and actionFGF, EGF; dimerization initiate signalling (autophosphorylation)
Autophosphorylation vs. transactivationautophosphorylation is same receptor type (RTK phosphorylating RTK); transactivation is 1 type of receptor activating another -> could be GPCR phosphorylating EGFR, could be RTK phosphorylating RTK)
Grb2 recognize a specific tryosine on the activated receptor how?through SH2 domain
Grb2 recruits Sos how?through SH3 domain which binds proline-rich section of Sos
Describe RasRas is a small G-protein (GTPase), not a kinase, it is anchored to the PM, it is NOT a heterotrimeric G-protein where it is associated with GPCR
Ras functioncell proliferation, differentiation, survival, apoptosis, gene expression
Rho function (incl. Rac)cytoskeleton dynamics
Rab functionmembrane and protein trafficking in the endocytic and secretory pathways
Arf functionvesicular trafficking, endocytosis, exocytosis [to bring things in]
Ran functionNucleocytoplasmic transport; mitotic spindle organization
SH1 domaincataytic domain of intracellular tyrosine kinases
SH2 domainrecognize specific phospho-tyrosine motifs
SH3 domainbinds to proline-rich domains in intracellular proteins
Srcproto-oncogenes, non-receptor tyrosine protein kinases; regulation of embryonic development and cell growth
proto-oncogene e.g. Src, Ras, Raf, causes normal cells to become cancerous when mutated
Compartmentalize MAPK signals by scaffolduse scaffold proteins to hold 3 kinases that compromise MAPK cascade, allows for precise recruitment & regulation of MAPK in cellular compartments pre-determined by nature of SCAFFOLD and RECEPTOR activating signal
How are GPCRs and RTK pathways related?GPCRs and RTKs have overlapping signal pathways for fine tuning of signal i.e. need ligand for both receptors to turn on certain transcription factors, modulate eachother's effects
PI 3Kinase (can bind phospho-tyrosine)Key regulator of cell survival
PTENphosphotase that inhibit Akt; in cancer, it is mutated (blocked)
Aktpromote cell survival
mTORcell survival, growth, proliferation
In cancer, EGFR is overexpressed (EGFR mutations): (2)ligand dependent signal amplification, ligand independent receptor homodimerize and activate
T/F - all lung cancer patient have mutated EGFR therefore high expression of EGFRF - not all lung cancer patients have mutated EGFR & not every lung cell expresses same receptor that is mutated (30% of patients had high EGFR expression, NOT ALL PATIENTS HAD HIGH EXPRESSION FO EGFR)
Cetuximab and Afatinib and siRNA treatment Cetuximab (monoclonal antibody) competes w/ EGF for EGFR binding, so prevent receptor homodimerization; Afatinib (small molecule), tyrosine kinase inhibitor so prevent activation by competing with ATP; both inhibit EGFR intracellular signalling (Akt, MAPK, STAT) and increase apoptosis. Combined treatment of SiRNA and EGFR inhibitory agent is ADDITIVE
Structuresingle pass transmembrane protein, carboxyl tail intracellular, amino tail extracellular
STAT (can bind phospho-tyrosine)transcription factor
PLC gamma (can bind phospho-tyrosine)leads to increased IP3 binding to IP3 receptor in ER, increasing Ca2+ and activating PKC
memorize

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