Chapter 16: Cell Signaling Flashcards
1
Q
Cell Signaling
A
the molecular mechanisms by which cells detect and respond to external stimuli and send messages to other cells
2
Q
Signal Transduction
A
- conversion of an impulse or stimulus from one physical or chemical form to another
- begins when incoming extracellular signal received and then produces an intracellular signal that alters cell behavior
3
Q
Examples of Extracellular signals acting slowly
A
- cell differentiation or increased cell growth and division
- slow, since they involve changes in gene expression and synthesis of new proteins(gene transcription and translation for a new protein)
4
Q
Examples of Extracellular signals acting rapidly
A
- cell movement, secretion, metabolism
- rapid, since there are NO changes in gene expression
5
Q
Explain the flexibility of a signal molecule
A
- the same signal molecule can induce different responses in different target cells
- info conveyed by the signal depends on how the target cell receives and interprets it
Example: acetylcholine can bind to heart pacemaker cells and salivary gland cells, but will create different responses(that could be exhibiting or inhibiting a process); it can bind to different receptor proteins than others
6
Q
Target cells
A
- possess proteins called receptors that recognize and respond to specific signal molecules-
7
Q
What 2 things do extracellular signal molecules bind to?
A
- cell surface receptors of target cell when the molecules are too large or hydrophilic; the cell surface receptor will generate one or more intracellular signaling molecules in target cell
- intracellular receptors in cytosol or nucleus when molecules are small enough or hydrophobic; regulates gene expression or other functions
8
Q
Receptor
A
- protein that recognizes and responds to a specific signal molecule
9
Q
Examples of cell surface receptors
A
- G protein coupled receptors
- enzyme coupled receptors
10
Q
Examples of intracellular receptors
A
- for NO, nitric oxide gas, receptor is guanylyl cyclase
- steroid hormones
11
Q
What does nitric oxide do?
A
- endothelial cells release it in response to acetylcholine secreted by nearby nerve endings
- it can trigger smooth muscle relaxation in blood-vessel wall
- locally acting gaseous signal molecule that diffuses across cell membranes to affect the activity of intracellular proteins
12
Q
Explain how protein guanylyl cyclase in smooth muscle cells relax
A
- neurotransmitter acetylcholine causes blood vessel to dilate by binding to a GPCR on surface of endothelial cells
- this activates G protein (Ga) to trigger Ca2+ release
- Ca2+ activates nitric oxide synthase (production of NO)
- NO diffuses out of endothelial cells into adjacent smooth muscle cells
- muscle cells relax (by regulating proteins)
activated by NO to relax! - catalyzes production of cyclic GMP from GTP
13
Q
Three main classes of cell-surface receptors
A
- ion channel-coupled receptors
- G-protein- couple receptors
- Enzyme-coupled receptors
14
Q
Ion channel coupled receptors
A
- change permeability of plasma membrane, thereby altering potential, and, if conditions are right, producing an electric current
- overall, opens in response to binding an extracellular signal molecule
15
Q
G-protein coupled receptors
A
- activate membrane-bound trimeric GTP-binding proteins (G proteins)
- activate or inhibit an enzyme or an ion channel in the plasma membrane, initiating intracellular signaling cascade
- an extracellular signal molecule binds, activated receptor signals trimeric G protein on cytosolic side of plasma membrane; turns on/off enzyme or ion channel
16
Q
Enzyme-coupled receptor
A
- act as enzymes or associated with enzymes inside the cell
- SINGLE trans-membrane spanning domain where the cytosolic domain either has intrinsic enzyme activity or associates directly with enzyme
- when stimulated, the enzymes can activate a wide variety of intracellular signaling pathways
- the extracellular signal molecule binds, enzyme activity switched on at other end of receptor; some have open activity, some rely on enzyme that becomes associated with activated receptor
17
Q
Describe the benefits of Enzyme coupled receptors
A
- promote growth, proliferation, differentiation and/or survivial(growth factors)
- responses are typically slow (hrs) and usually require many intracellular signalling steps
- may have direct repid effects on cytoskeleton controlling the way a cell moves or changes its shape such as neuronal growth to a specific target
18
Q
Describe how cell surface receptors work
A
- protein activates one or more intracellular signaling pathways
- each pathway is mediated by a series of intracellular signaling molecules (proteins or small messenger molecules)
- a message passed downstream; primary step is protein recognizes an extracellular signal molecule and generates a diff. type of intracellular signaling molecule in response
- message is passed until action of metabolic enzyme, cytoskeleton changes to new configuration, or gene switched on/off(alters behavior)
19
Q
Enzyme coupled receptors: RTKs
A
- Receptor tyrosine kinases
- most RTKs acticates the Monomeric GTPase Ras
- transmembrane proteins that display their ligand binding domains on outer surface of plasma membrane
- cytoplasmic domain of receptor either reacts as an enzyme, or forms complex with another protein that acts as an enzyme
20
Q
What does activation of an RTK do?
A
- it stimulates the assembly of an intracellular signaling complex
21
Q
SH_2 Domain
A
- recognizes and binds to specific phosphorylated tyrosines or cytosolic tail of an activated RTK or another intracellular signaling protein
22
Q
Describe the process of Receptor Tyrosine Kinases
A
- when a signaling molecule binds to this receptor, the receptors dimerize
- the dimer can physically cross-link two receptor molecules
- dimer formation brings the kinases domain of each cytosolic receptor tail into contact with the other, kinases will phosphorylate several tyrosines on adjacent receptor tail
- each phosphorylated tyrosine creates docking sites for downstream signaling molecules to bind, helps relay messages to cell interior
- (proteins with SH2 domains bind to phosphorylated tyrosines on the receptors
23
Q
Ras
A
- small GTP-binding protein that is attached by a lipid tail to the cytosolic face of the plasma membrane
- a family of monomeric GTPases
- helps relay signals from cell surface receptors to the nucleus
- activated in pathways involved in cell proliferation
-protein contains covalently attached lipid group that helps anchor the protein to the inside of the membrane
24
Q
Explain the process of activation of Ras
A
- RTKs activate Ras
- adaptor protein docks on particular phosphotyrosine on activated receptor(serve as docking sites for target proteins with phosphotyrosine binding domains/Src Homology Domains)
- adapter recruits Ras guanine nucleotide exchange factor (Ras GEF) that stimulates Ras to exchange its bound GDP for GTP
- activated Ras protein can now stimulate several downstream signaling pathways
25
Q
MAPK and its importance
A
- Mitogen Activated Protein Kinase signaling pathway
- tyrosine phosphorylation and Ras activation short lived, Ras acitvation of MAP kinase critical to covert short-lived events into longer lasting ones
- longer lasting events that can sustain signal and relay it to nucleus to alter gene expression; acheived by series of serine/threonine phosphorylations
26
Q
Function of MAPK
A
- three functionally interlinked protein kinases that allow cells to respond to extracellular signal molecules that stimulate proliferation by activation of specific sets of gene transcription factors
- MAP kinase, MAP kinase kinase, and MAP kinase kinase kinase
27
Q
MAP kinase
A
- mitogen activated protein kinase
- signaling molecule that is final kinase in 3-kinase sequence
28
Q
Specific function of final MAP kinase
A
- phosphorylates effector proteins and certain transcription regulators
- creates change in gene expression(stimulate cell proliferation, promote cell survival, or induce cell differentiation; depends on active genes and signals received)
29
Q
Describe how Ras activates the MAP-kinase Pathway
A
- activation begins with MAP-kinase-kinase kinase (Raf), it activates MAP-kinase-kinase (Mek), which activates MAP-kinase Erk
- Erk phosphorylates a variety of downstream proteins, including other kinases, as well as gene regulatory proteins in the nucleus
- result changes gene expression and protein activity, causes complex changes in cell behavior
30
Q
PI 3-kinase
A
- phosphionositid 3-kinase
- enzyme that phosphorylates inositol phospholipids in the plasma membrane, generating docking sites for intracellular signaling proteins that promote cell growth and survivial
- RTKs also activate PI 3-kinase tp produce lipid docking sites in the plasma membrane
31
Q
Describe importance of RTKs activating the PI 3-Kinase Pathway
A
- in parallel with MAPK activation, RTKs also activate the PI 3-K signaling pathway for stimulating cell growth and survival
32
Q
Describe the PI 3-Kinase Pathway
A
- extracellular signal activates FTK
- RTK activates PI 3-Kinase
- PI 3-Kinase phosphorylates an insitol phospholipid embedded in cytosolic side of plasma membrane
- phosphorylated IP attract intracellular signal proteins that have interaction domain to recognize IP
- signal protein Akt is protein kinase that activated at the membrane by phosphorylation mediated by 2 other protein kinases (1 and 2)
- kinase 1 recruited by phosphorylated lipid docking sites
- once Akt activated, releases from plasma membrane, phosphorylates downstream proteins on specific serines and threonines
33
Q
Describe the relationship between Akt and Tor
A
- Akt stimulates cells to grow in size by acitvating the serine/threonine kinase Tor
- (binding of growth factor to an RTK activates the PI 3-Kinase signaling pathway above; Akt indirectly activates Tor by phosphorylating and inhibiting protein that keeps Tor inactive)
- Tor stimulates protein synthesis, and/or inhibits protein degredation by phosphorylating key proteins in these processes
34
Q
rapanyein
A
- anticancer drug that slows cell growth by inhibiting Tor
35
Q
Ephrin receptors
A
- group of receptors that are activated in response to binding with Eph receptor-interacting proteins (Ephrins)
-RTKs
neuron pathfinding during development relies on RTKs, specifically these in this case - Ephrin Receptors are coupled to Rho family GTPases couple receptors to the cytoskeleton
36
Q
Process of Ephrin receptors
A
- Rho Family GTPases couple cell surface receptors to the cytoskeleton
- Eph RTK on surface of motor neurons helps guide migrating axon (growth cone) to muscle target
- binding of a transmembrane ephrin protein to Eph receptor caues growth cone to collapse, repelling axon from inappropriate regions
37
Q
What happens if growth of neurons is altered? Or connections are altered?
A
- can get cross-talk between different signalling systems, like vision, hearing and learning & memory
- changes in ephrins or ephrin receptors can cause synesthesia
38
Q
Synesthesia
A
- condition which otherwise normal people experience the blending of two or more senses
- skeptical phenomenon until recently
- occurs possibly from cross activation, in which two normally separate areas of the brain ellicit activity in each other
- explores the general processes in brain sensory info and uses it to make abstract connections
