The purpose of signal transduction is ______ ______ - What are the 5 responses to signals?
Information transfer - 1) cell survival 2) cell division 3) alteration in metabolic 4) differentiation 5) cell death
What are the three membrane receptors? What are the two non-membrane receptors
1) Chemical signals and receptors 2) G linked protein receptor 3) Protein kinase receptor - 1) Nitrous oxide 2) Steroid hormones
What are the two chemical messengers found in the nervous system? What are the two chemical messengers found in the endocrine system? What are the two chemical messengers found in the immune system? What are the the three eicosanoids? Give three examples of growth factors as chemical messengers (there are many)
Biogenic amines and neuropeptides - Proteins and steroid hormones - Cytokines and interleukins - Prostaglandins, thromboxanes, leukotrines - FGF, PDGF, EGF
What is the fastest mode of extracellular signaling? Give an example of this - _____ hormones are released into the bloodstream - ______ signaling is a way for cells to affect the behavior of neighboring cells - What is autocrine signaling? What is this important for? ____ signaling is also known as contact dependent signaling - Why? - Which signaling is found in the nervous system? Which two of the above extracellular signals are important during embryonic development?
Direct signaling - cardiac muscle cells via gap junctions - Endocrine - Paracrine - A way for a cell to alter its own extracellular environment - Growth - Juxtacrine - Because two adjacent cells must make physical contact in order to communicate - Synaptic - Paracrine and Juxtracrine
Which signals bind to extracellular receptors (2)? Which signals bind to internal receptors (2)?
Non steroids and proteins - Steroid molecules and nitric oxide
What are the three domains that comprise a cell surface receptor?
1) Extracellular domains/receptor binding site 2) Transmembrane domain 3) Cytoplasmic or intracellular domains
What does calcium target? Upon binding, what does this complex activate (2)? What cleaves PIP 2? What does IP3 lead to? ___ and ___ both activate DAG which initiates ____ ____ ____ - ____ and ____ target protein kinases
Calmodulin - Protein kinases and phosphatases - Phospholipase C - Calcium to be released from the Smooth endoplasmic reticulum - Diacylglycerol (DG) and Ceramide, Protein Kinase C - cAMP and cGMP
What do enzymes do as secondary messengers? What activates protein kinases as a second messenger target (3) - What does it lead to? What affect does protein phosphatases have? What activates them?
Modulate phosphorylation - Calcium, cAMP, DAG - Increased phosphorylation - Decrease phosphorylation - Ca/calmodulin complex
Which subunit of the G protein receptor carries GTPase activity? What is an example of this receptor?
Alpha - Beta-adrenergic receptor that mediates the effects of epinephrine on many tissues
What receptors do heterotrimeric G proteins use? How about monomeric G proteins? What is the superfamily of monomeric G proteins called? Which type of G protein is used to regulate second messengers?
G-protein linked receptors - Catalytic receptors - Ras superfamily - Heterotrimeric G proteins
Outline the steps involved when a ligand binds to a G protein receptor
Normally, the alpha subunit is bound to GDP and has an affinity for the beta and gamma subunits -> When a ligand binds, the alpha subunit ditches GDP for GTP, leading to a dissociation -> The dissociated alpha subunit then binds to a nearby unit, activating it - GTP is then hydrolyzed to GDP and the alpha subunit reunites with the beta and gamma subunits
What are the five classes of G proteins? Include what each activates!
1) Gs -> Adenylyl Cyclase -> Increase cAMP
2) Gi -> Adenylyl Cyclase -> Decreased cAMP
3) Gq -> PI-PLC -> IP3 + DAG
4) Go -> ion channels
5) Gt -> cGMP PDE -> cGMP -> Rhodopsin in Rods of Retina
Outline the steps involved when epinephrine binds to a G protein coupled receptor - what eventually stops this process?
Alpha G activates Adenylyl Cyclase which forms cAMP -> activates pKA causing signal transaction cascade - cyclic nucleotide phosphodiesterase
Which factors stimulate Adenylyl Cyclase (3)? Which factors inhibit it (3)?
Glucagon, beta-adrenaline, ACTH - alpha adrenaline, angiotensin 2, acetylcholine
What is the effect of cholera toxin? - What is the clinical symptom?
Targets Gs and always turn the cell on - this leads to stimulation of AC so there is high cAMP in cells - Diarrhea
What is the effect of Purtussis toxin? What is the clinical symptom?
Targets Gi to keep cell off, AC cannot turn off now, so there is high cAMP in cells - Allergy of histamine
Which G protein receptor is used in calcium mediated signal amplification? Outline the steps
Alpha G activates Phospholipase C which cleaves PI into IP3 and DAG - IP3 binds to calcium channel is endoplasm reticulum - DAG activates protein kinase C
Cell functions regulated by IP3 and DAG chart
Where are Go channels found (2)? Which ions are often used? (4)?
CNS neurons and atrial myocytes - K, Ca, Na, Cl
What are the two ION channels found in motor end plates? How does each work?
1) Voltage gated ion channel - depolarization of synaptic terminal open calcium gated channels and they diffuse into the cell 2) Ligand Gated ion Channels - 2 molecules of ACh bind to receptor and open ion channel causing sodium ions to diffuse in and K ions to diffuse out
How is reversibility guaranteed for ion channel receptors?
By pump ions back out using a separate protein
Besides in the synaptic cleft, what is the best example of a ligand gated ion channel?
What are the major ligands used to bind to RTKs? (6) - Which terminus is extraceullar? Which is cytoplasmic?
EGF, VEGF, FGF, NGF, PDGF, Insulin - N, C
*What are the classes of receptors that activate TRKs? (3 w/ details)
1) Adapter Proteins (SH2 domain) - RAS (i.e. MAP kinase pathway to nucleus) and STAT (signal transducers and activators of transcription to nucleus for transcription of genes for cell growth and differentiation) 2) PI3 Kinase Pathway for cell survival using EGF 3) Insulin receptor
What recognizes the phosphorylated tyrosines?
Adaptor proteins with SH2 domains
What kind of receptor is used in Ras activation? What is the name of this pathway? Outline the steps - What is the final outcome?
RTK- MAP Kinase Pathway - Ras->Raf->Mek->Erk to the nucleus-> transcription factors - Transcription of proliferating genes including cyclinD
What type of receptor does the PI3 kinase pathway use? What are the names of the proteins involved in this pathway? Which is to prevent apoptosis and promote cell survival? What needs to be mutated to keep PI3 kinase constantly active and cause cancer?
RTK - PI3, PIP2, PIP4, PTEN, AKT, BAD - BAD - PTEN
What type of receptor does insulin bind to? What protein is activated by the dimerization of these receptors? Activation of that protein does which three things (3)
RTK - IRS - 1) Activates Ras/MAP Kinase Pathway 2) Activates PI3 Kinase 3) Activates Phospholipase C
Which four effects get stimulated by insulin binding?
1) Glucose uptake 2) Glycogen synthesis 3) Protein synthesis 4) Fat synthesis
Which pathway does NOT use tyrosine residues? What is the relative speed difference as a result? What uses this pathway (2)? For what?
JAK-STAT - faster - Cytokines and Interleukins - immune cell proliferation
What are cytokines? What are the designed to do? What do they release (4)?
Messengers of immune system - kill microorganisms - 1) interleukins 2) tumor necrosis factor 3) interferons 4) colony stimulating factors
What type of receptors are TGFBeta receptors? What proteins do they use? What do they induce/what is their purpose (4)? What are their ligands (4)?
Serine/Threonine Receptors - SMAD proteins - 1) Cell proliferation and death 2) Cell differentiation 3) Tissue repair 4) Immune regulation - 1) Bone morphogenic proteins (BMPs) 2) Growth and differentiation factors (GDFs) 3) Anti-mullerian hormones (AMH) 4) Activin, Nodal, and TGFBetas
Explain how a TGFbeta receptor works
TGFBeta ligand binds to a type 2 receptor -> this serine/threonine receptor kinase catalyzes the phosphorylation of type 1 receptor (4 total receptors here) -> SMAD is phosphorylated and binds to SARA -> this phosphorylated complex enters the nucleus and causes transcription of DNA
What are the two types of receptors that can induce the MAPK pathway? - What does the MAPK pathway control (4)?
1) RTK 2) TGFbeta using serine/threonine kinases - cell growth, differentiation, transformation, apoptosis
What are the three types of NO that relaxes arterial smooth muscle? What ligand starts this process? Where are the G linked protein receptors found that initiate this process (4)? What actually creates NO, at this point, where does it travel to via gaseous diffusion - What does NO activate? What inactivates NO activity?
eNOS, iNOS, nNOS - Acetylcholine/Bradykinin - Plasma membrane, mitochondria, golgi apparatus, cytoplasm - NO synthase - smooth muscle cell from endothelial cell - Guanylyl Cyclase -> cGMP -> GMP - Phosphodiesterase
Which 2 drugs are given in patients lacking NO? What modulates CFTR in response to infection?
Nitroglycerin and Sildenafil (viagra) which inhibits cGMP phosphodiesterase, enhancing the dilatory effects of NO - cGMP
Where are integrins found? What do they play a role in (4)? What type of activity do they not participate in? Which cells express integrins in circulation? Why?
Epithelial cells - attachment of cell to ECM, signal transduction, adhesion to stromal cells, survival and differentiation - kinase activity - Circulating blood cells (white blood cells) - so they can attach to endothelial cells and travel to the site of infection