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41 Cards in this Set

  • Front
  • Back

basics of intracellular signaling

1. extracellular signal molecule


2. receptor protein


3. intracellular signaling proteins


4. effector proteins

4 forms of intracellular signalling

1. contact-dependent


2. paracrine


3. synaptic


4. endocrine

endocrine signalling

1. long range


2. travels via bloodstream


3. hormones and endocrine glands

synaptic signalling

1. neurons


2. synapses directly with target cell


3. neurotransmitters

contact dependent signalling

1. cell-to-cell


2. membrane bound signal molecule


3. ex: Notch and Delta proteins

Notch protein

will develop into a neuron

Delta protein

inhibitory signal that prevents neuronal development (becomes a glial cell)

gap junction structure

connexins --> connexons --> intercellular channels

connexons

can be homomeric or heteromeric

intercellular channels

can be homotypic or heterotypic

roles of extracellular signal molecules

1. survive


2. grow and divide


3. differentiate


4. die

multiple roles for individual signaling molecuels

1. acetylcholine


2. heart muscle cell


3. skeletal muscle cell


4. salivary gland cell

three major classes of cell-surface receptors

1. ion-channel coupled receptors


2. G-protein coupled receptors


3. enzyme-coupled receptors

actions of intercellular signaling pathway

1. relay to component


2. scaffold to bring signaling proteins together


3. transduce signal --> stimulate response


4. amplify signal --> large response


5. integrate signals from multiple pathways


6. spread signal to different pathways


7. anchor proteins to structure where needed


8. modulate other proteins to regulate signal strength


G-protein coupled receptors

1. consist of a single polypeptide chain that passes through the bilayer 7 times


2. use GTP binding proteins to relay signal into cell interior

trimeric G-proteins

1. relay signals from GPCRs


2. binding of ligand induces conformational change


3. activates trimeric GTP-binding proteins

cyclic AMP

1. intracellular mediator


2. changes in AMP concentration alters gene transcription

protein kinase

mediates effects of cyclic AMP

GPCRs

regulate intracellular calcium levles

effector proteins

1. metabolic enzyme (altered metabolism)


2. gene regulatory protein (altered gene exp)


3. cytoskeletal protein (altered cell shape or movement)

contact-dependent signaling

paracrine signaling

synaptic signaling

endocrine siganling

contact-dependent signaling

gap junction

gap junction

1. allow exchange of inorganic ions & small water soluable molecules


2. does not allow for exchange of proteins or nucleic acids


3. communication can occur in both directions


4. typical signals transmitted: Ca++ or cAMP

connexins

connexons

signaling factor gradients 

signaling factor gradients

intercellular channels

intercellular channels

intracellular receptors

specify cell fate

NO intracellular signaling

*

NO intracellular signaling pathway

1. activated nerve terminal


2. release Ach


3. Ach binds to and activates NOS on EC


4. arginine signaling generates NO


5. rapid diffusion of NO across membranes


6. NO bound to guanylyl cyclase


7. signals GTP --> cGMP


8. rapid relaxation of smooth muscle cell

NOS

NO synthase

inactive G protein

synthesis and degradation of cAMP

synthesis and degradation of cAMP

activated G protein

LEFT

ATP -- adenylyl cyclase --> cAMP --> cAMP phosphodiesterase --> 5' -AMP

RIGHT

RIGHT

1. inactive form


2. regulatory subunit


3. cAMP binding sites

what happens when changes in cAMP concentration occurs?

what happens when changes in cAMP concentration occurs?

1. inactive catalytic subunit


2. becomes active when cAMP binds to regulatory subunits

GPCRF intracellular Ca regulation pathway

alteration of gene transcription

GPCR intracellular Ca regulatory pathway

1. signal molecule binds/activated GPCR


2. activated Gq protein


3. activated phospholipase C-Beta


4. PI 4,5-biphosphate [PI(4,5)P2]dissociates into diacylglycerol AND inositol 1,4,5-trisphosphate (IP3)


5a. IP3 bidns to lumen of ER


5b. diacylglycerol binds to inactive protein kinase C


6a. Ca++ opens IP3-gated Ca++ release channels


7a. Ca++ released from ER lumen


8a. Ca++ binds/activates protein kinase C