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Cell Biology: Final > Chapter 16: Cell Signaling > Flashcards

Chapter 16: Cell Signaling Flashcards

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1
Q

Cell Signaling

A

the molecular mechanisms by which cells detect and respond to external stimuli and send messages to other cells

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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
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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)
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4
Q

Examples of Extracellular signals acting rapidly

A
  • cell movement, secretion, metabolism
  • rapid, since there are NO changes in gene expression
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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

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6
Q

Target cells

A
  • possess proteins called receptors that recognize and respond to specific signal molecules-
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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
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8
Q

Receptor

A
  • protein that recognizes and responds to a specific signal molecule
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9
Q

Examples of cell surface receptors

A
  • G protein coupled receptors
  • enzyme coupled receptors
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10
Q

Examples of intracellular receptors

A
  • for NO, nitric oxide gas, receptor is guanylyl cyclase
  • steroid hormones
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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
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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
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13
Q

Three main classes of cell-surface receptors

A
  • ion channel-coupled receptors
  • G-protein- couple receptors
  • Enzyme-coupled receptors
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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
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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
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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

Cell Biology: Final (6 decks)

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