Cell Signaling Flashcards
_____ molecules work in combinations to regulate the behavior of the cell. Cells require signals to ____ and ____. _____, or programmed cell death will occur if a cell does not receive appropriate signals
Signal
Survive
Divide
Apoptosis
____ ____ (_____): signaling requiring physical contact between cells.
_____: cells signaling to themselves
____: cells signaling to neighbor cells
_____: signaling to distant cells usually via secreted hormones
Contact dependent (Juxtacrine)
Autocrine
Paracrine
Endocrine
A ____ is a signaling molecule produced by one cell that binds to a receptor on either the same or another cell
Ligand
A _____ becomes activated by a Ligand resulting in receptor driven changes in Intracellular protein-protein interactions and/or enzyme activity. This is referred to as ____ ___
Receptor
Signal transductions
Signal transduction results in the activation or release of other small Intracellular molecules called ____ ___. Ex: cAMP, cGMP, IP3, DAG, Ca++
Second messengers
If a signaling molecule is hydrophilic it will most likely bind to _____ receptors. If a signal molecule is hydrophobic it will most likely bind to ____ receptors.
Extracellular
Intracellular
Hydrophobic signal molecules can ____ across the plasma membrane to bind to receptors inside the cell, usually in the ____ or ____.
Such signals are generally transported into the blood stream and other extracellular fluid via _____ proteins and then dissociate before entering the target cell.
Diffuse
Cytoplasm
Nucleus
Carrier
Different cells respond differently to the ___ signal molecule due to different receptors, different signal transduction, different second messenger. An example of this is _____, it decreases contraction of cardiomyocytes but stimulates contraction in skeletal muscle
Same
Acetylcholine
____ ____ loops occur if an upstream molecule regulates a downstream target through two or more separate mechanisms or pathways
Feed forward
___ ___ loops amplify a response through the ability of a product to increase the activity of an earlier component of the pathway
Positive feedback
____ ___ loops limit a response by the ability of a product to inhibit the activity of an earlier component of the pathway
Negative feedback
____ ____ vary in strength with the signal molecule concentration. These types are particularly evident during ___ ___, when the organization of the body plan is being determine. Example: ____ in low levels promotes blood cell differentiation, whereas in high levels it promotes muscle differentiation
Graded response
Early development
Activin
______ ____ are signals that turn on and off which suddenly and rapidly change cell behavior. Example: the decisions in cell division and regulated cell death
Switch-like responses
What mechanisms determine weather the response is graded or switch like?
The concentration of a molecule can be adjusted rapidly only if it’s half life is ____
Short
The response increases with an ____ in the number of effector molecules that must bind simultaneously to activate a target
Increase
Switch like functions in a cell signaling pathway can involve _____ or ____.
Phosphorylation
G proteins
G proteins are activated by ___ and inactivated by ____. Two major categories include ____ G proteins which relay signals from G protein linked receptors. _____ G proteins regulate multiple Intracellular events
GTP
GDP
Trimeric
Monomeric
Many cells must ___ signals from multiple sources to fine tune their responses. This is accomplished through _____ proteins which receive multiple inputs
Integrate
Integrator
_____ help reorganize signaling complexes. They contain multiple sites for protein docking and can organize individual components into a signaling ____. This can enhance the speed, efficiency, and specificity of the response
Scaffolds
Complex
____ ____ ____ facilitate the assembly of signaling networks. Each of these compact protein modules bind to a particular structural ____ in the protein with which a signaling protein interacts. This allows signal proteins to bind to one another in multiple combinations resulting in ___ ____ of interactions
Modular biding domains
Motifs
3D networks
____ ____ is the decreased responsiveness that occurs with repeated or chronic exposure to an agonist, it is a general feature of most signaling membrane receptors
Receptor desensitization
_____ ____ is characterized by a decrease in total receptor numbers due to endocytosis and subsequent degradation of the receptors, caused by long term exposure to agonist
Receptor downregulation
Mechanisms to limit signaling:
What are the 4 types of extracellular signaling pathways?
3 types of ion channels:
____-gated
____-gated
_____-gated
Ligand
Voltage
Mechanically
Ligand gated ion channels open and close to allow for regulated ion passage. ______ signaling is when a ligand acts directly on the ion channel (faster). _____ signaling is when a ligand acts on a receptor which indirectly modulates ion channels (slower)
Ionotropic
Metabotropic
Ionotropic and metabotropic signaling play an important role in _____ signaling.
Neuronal
____ gated ion channels open and close in response to changes in membrane voltage
____ gated ion channels open and close in response to physical forces such as stretch, shear, or compression. Associated with multiple sensory functions including hearing and touch
Mechanically
_____ are the largest family of cell surface receptors
G proteins
G protein coupled receptors (GPCRs) interact with heterotrimeric G proteins composed of ___, ___ and ___ subunits
Alpha, beta, gamma
In the ______ state, alpha subunit has GDP bound.
Binding of a signal molecules changes the conformation of the ____ which can then act as a _____ and exchange GDP for GTP. This activates the alpha subunit
Unstimulated
GPCR
GEF (GTP exchange factor)
Once the aloha subunit is activated, this causes the ____ to dissociate into two active units: ____ subunit and the ____ complex
Trimer
Alpha
Beta-gamma
When the alpha subunit binds to target proteins in activates it or inactivates it. Once the alpha subunit hydrolyzes ____ to ____, It dissociates from the target and rebinds to ____ complex, reforming the inactive timeric G protein
GTP
GDP
beta-gamma
Three important pathways regulated by GPCR signaling:
____ ____ pathway produces cAMP and turns on protein kinase A (PKA). PKA regulates ____ and ____ metabolism
Adenylate cyclase
Glycogen
Lipid
______ __ hydrolyzes P1P2 forming IP3 and diacylglycerol (DAG), which raises cytoplasmic _____ and activates protein kinase C (PKC). PKC regulates _____ ____ and ___ ____.
Phospholipase C
Ca++
Cell proliferation
Gene expression
____ monomeric G protein family members (Rho, Rac, and Cdc42) which regulate ____ and cell ____.
Rho
Cytoskeleton
Motility
GPCR continues to act as a GEF for trimeric G protein complexes until turned off. ____ and ____ phosphorylation of GPCRs inhibits their signaling, ____ feedback loop.
_____ also phosphorylates GPCRs allowing ______ to bind and promote ubiquitination and proteolysis
PKA and PKC
GRK (GPCR kinase)
Beta-arrestin
Receptors that are tyrosine kinases: ____
Receptors that recruit tyrosine kinases:
Receptors that are serine-threonine kinases:
Receptor guanylyl cyclases:
Focal adhesions have mechanosensing and signal functions which involve two non receptor tyrosine kinases - ____ and ____. These influence cell adhesion, cell motility, and proliferation
FAK
Src
FAK and Src influence numerous other signaling pathways including:
mTOR regulates many processes that are involved in cell ___ and ____ when metabolic and nutritional conditions are favorable. Two complexes ____ and ___.
____ inhibits mTOR activity. ______ inhibits TSC complexes, upregulating mTOR synthesis
Survival
Growth
mTORC1 and mTORC2
TSC (tuberous sclerosis complex)
PKB/Akt
4 signaling pathways associated with proteolytic events:
Notch signaling ligands are ___ and ___, transmembrane proteins located on adjacent cells. Binding triggers _____ of Notch, releasing the cytosolic ___ inside the cell. The tail goes into the ____ to activate gene expression
Delta and Jagged
Proteolysis
Tail
Some nuclear receptors reside in the cytoplasm and move to the ___ to initiate transcription upon steroid Ligand binding. Others reside in the ____ already bound to DNA and initiate transcription upon metabolite ligand binding
Nucleus
Nucleus
Nuclear hormone receptor activation can result in multiple waves of ___ ___. They can trigger stimulatory and inhibitory ___ ___.
Gene expression
Transcription factors
What types of signaling pathways could this represent:
Nuclear hormone receptor
Estrogen signaling
Ligands are small, hydrophobic molecules
Metabotropic ion channel
Slow and sustained ligand gated ion channel
Involves G protein linked receptors
G protein linked receptor
Enzyme linked receptor
Representing growth factor signaling G1
Ionotropic ion channel
Fast and transient ligand gated ion channel
Proteolysis linked receptor
Notch pathway
Two types of induction:
______ uses a secreted molecule that diffuses from one cell to another
_____uses direct cell contact
Paracrine
Juxtacrine
Only cells that have the right ____ can respond to a Paracrine signal. Example in eye cells: only the head ectoderm can respond to the optic vesicle, lens is formed in the correct location
Receptor
Mammalian development can be thought of as a series of ____ induction. Neighbor cells produce Paracrine factors that affect other neighbor cells and so on
Sequential
A concentration gradient:
the secreted signaling factors act on distant cells and form a gradient which affects cells differently depending on the _____ of the signaling factors. Secreted signaling factors _____ Intracellular signaling pathways often leading to _____ regulation to derive diverse cell types
Concentration
Activate
Transcriptional
In the absence of SHH, Gli is ____ and acts as a transcriptional ____. When SHH is present, Gli is not ____ and acts as a transcriptional ____.
Cleaved
Repressor
Cleaved
Activator
Cranial caudal axis patterning in the limb is dependent on ____ expressed in the ZPA. ____ creates a ____ and the cells closest to the ZPA get the highest concentration of signal, and will have the highest ____ activator to ____ repressor ratio and will adopt the pinky identity
SHH
SHH
gradient
GLi activator to GLi repressor ratio
Laurin-sandrow syndrome a ZRS associated syndrome show mirror image limbs as a result
TGFbeta signaling pathway uses _____ to regulate transcription factor localization and activity for differential gene expression
Phosphorylation
Opposing SHH and BMP gradient induces the ____ transcription factors expression along the D/V axis of neural tube
Differential
Summary of dorsal-ventral patterning of the neural tube:
____ patterning is heavily dependent on the actions and gradients of siffusbke Paracrine signals
Embryo
Take home message
