Term
| what four components make up a signal transduction pathway? |
|
Definition
1. extracellular signaling molecule
2. receptor
3. intracellular signaling pathway
4. final target proteins |
|
|
Term
| what are the targets of fast signal responses? what are the targets of slow signal responses? |
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Definition
fast- allosterically regulate (phosphorylate/dephosphorylate) enzymes in the cell
slow- affect (activate/deactivate) txn factors to cause changes in gene expression |
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|
Term
| why must a signal always be inactivated after a certain period of time? |
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Definition
-limits the response to the signal to a specific time and space
-makes sure cells dont overact
-allows them to respond appropriately to next incoming signal |
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|
Term
| true or false: hormones are part of the paracrine system |
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Definition
| false. hormones are part of the endocrine system and local mediators are part of the paracrine system |
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|
Term
| which extracellular signaling molecules are considered public messages (not targeted to specific cells) and which are private messages (only heard by one or a few specific cells)? |
|
Definition
| hormones and local mediators are public messages and neursotransmitters and contact-dependent signaling molecules are private messages |
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Term
| ____________ are extracellular signals that travel throughout the body through the blood and _______________ are extracellular molecules that travel to nearby cells in the extracellular fluid |
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Definition
| hormones, local mediators |
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|
Term
| growth factors are an example of a ___________________ |
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Definition
|
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Term
| which type of extracellular signaling molecule is part of a cells membrane (glycolipid or glycoprotein) and thus only affects neighboring cells |
|
Definition
| contact-dependent signaling molecules |
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Term
| most extracellular signaling molecules are (hydrophilic/hydrophobic/small polar) and thus (require/dont require) transmembrane receptors |
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Definition
| most are hydrophilic and thus do require transmembrane receptors but there are also hydrophobic and small polar examples as well which diffuse through the plasma membrane |
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Term
| ___________ is a small, polar molecule that is secreted by Ach-bound endothelial cells and is used as a signal to control blood pressure and blood flow |
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Definition
|
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Term
| true or false: nitric oxide signals smooth muscles to contract and thus decrease blood flow |
|
Definition
| false. it signals them to relax and increase blood flow |
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Term
| when NO enters a smooth muscle cell (via passive diffusion through the membrane)it targets _________________ which then breaks down into _______ and _______ |
|
Definition
| guanylyl cyclase, GTP, cAMP |
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Term
| true or false: steroid hormones must be bound to a carrier protein when traveling through the blood |
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Definition
|
|
Term
| what is the structure of a steroid hormone? from which molecule are they derived? |
|
Definition
| ring structure, derived from cholesterol |
|
|
Term
| what are the common targets of steroid hormones? |
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Definition
|
|
Term
| true or false: steroid hormones require a TM receptor to enter a cell |
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Definition
| false. steroid hormones are lipid soluble and will enter the cell via passive diffusion after being released from their carrier protein |
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|
Term
| what are four ways to stop an extracellular signal response? |
|
Definition
1. degrade the extracellular signal outside the cell
2. covalently modify the signal so it can no longer bind to the receptor
3. endocytose the receptor with bound signal
4. bind cytoplasmic inhibitor to receptor (via feedback from a downstream pathway) |
|
|
Term
| what are four ways to stop an extracellular signal response? |
|
Definition
1. degrade the extracellular signal outside the cell
2. covalently modify the signal so it can no longer bind to the receptor
3. endocytose the receptor with bound signal
4. bind cytoplasmic inhibitor to receptor (via feedback from a downstream pathway) |
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|
Term
| _______________ are small, diffusible, non-protein molecules usually found in the cytoskeleton that act as allosteric regulators |
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Definition
|
|
Term
| what synthesizes 2nd messengers? |
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Definition
| enzymes that are part of signaling pathways (except Ca++) |
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|
Term
| cAMP is synthesized from ATP by __________________ and degraded to AMP by ________________________ |
|
Definition
| adenylyl cyclase, cAMP phosphodiesterase |
|
|
Term
| what is one target of cAMP? |
|
Definition
|
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Term
| 2nd messengers, cAMP, G-proteins and inositol phospholipids are all examples of _______________ |
|
Definition
| intracellular signaling molecules |
|
|
Term
| what happens when PIP2 (an inositol phospholipid) is cleaved by phospholipase C? |
|
Definition
| it forms DAG (diaglycerol) which stays in the membrane and IP3 (inositol 1,4,5-triphosphate) which diffuses through the cytoplasm and opens Ca++ channels in the ER. signal is turned off when both DAG and IP3 are degraded by enzymes in the cell. |
|
|
Term
| where is Ca++ stored in the cell? |
|
Definition
|
|
Term
| what are two targets of Ca++? |
|
Definition
|
|
Term
| true or false: Ca++ is constitutively pumped into the ER and out of the cell by transporter proteins |
|
Definition
|
|
Term
| where does the energy for Ca++ transport come from? |
|
Definition
|
|
Term
| the acetylcholine receptor in skeletal muscles is what type of receptor? |
|
Definition
| ion channel linked receptor (or ligand-gated channel) |
|
|
Term
| what is the structure of an ion channel linked receptor? |
|
Definition
| has multiple subunits that come together to from a channel that is opened/closed with binding of an exracellular molecule (ligand) |
|
|
Term
| what type of receptor is made up of 7-pass transmembrane proteins? |
|
Definition
| G-protein-linked receptor |
|
|
Term
| what happens when a ligand binds to a G-protein-linked receptor? |
|
Definition
| there is a change in helical packing (tertiary structure change) which leads to a conformational change of the receptors intracellular domain. this change releases GDP from G(alpha subunit) and allows GTP to bind. both subunits are released from the receptor and leave to bind downstream proteins |
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|
Term
| what are three possible targets for trimeric G-proteins? |
|
Definition
| ion-channels, adenylyl cyclase, phospholipase C |
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|
Term
| _____ and ______ together act to activate PKC at the membrane |
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Definition
|
|
Term
| _____________ receptors are made up of single pass transmembrane proteins and are dimerized when bound by a ligand |
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Definition
|
|
Term
| what is an example of an enzyme-linked receptor? |
|
Definition
| tyrosine kinase-linked receptor in which ligand binding leads to dimerization and cross-phosphorylation of tyrosines which other downstream proteins bind to and become active |
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|
Term
|
Definition
| a monomeric G-protein that is activated via adaptor proteins activated by growth factor bound tyrosine kinase-linked receptors. this protein activates the MAP-kinase cascade and leads to cell division. |
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|
Term
| G-proteins can be _____________, have one subunit or _____________, have three subunits |
|
Definition
|
|
Term
| what are the 2 main classes of kinases? |
|
Definition
| Ser/Thr kinases and Tyr kinases |
|
|
Term
| how do kinases exhibit target specificity? |
|
Definition
| they bind to a recognition site on target protein made up of amino acids near the Ser, Thr or Tyr to be phosphorylated |
|
|
Term
| what is the difference in effect of phosporylation of a Ser/Thr vs. a Tyr |
|
Definition
Ser/Thr phosphorylation activates or inhibits a protein
Tyr phosphorylation allows binding and activation of downstream targets (protein complexes) |
|
|
Term
| (kinases/phosphotases) are regulated whereas (kinases/phosphotases) are constitutively active |
|
Definition
|
|
Term
| when GDP-bound G-proteins are (active/inactive) |
|
Definition
|
|
Term
| __________ turn G-proteins on by promoting exchange of GTP for GDP and __________ turn G-proteins off by increasing the rate of GTP hydrolysis |
|
Definition
| GEF's (guanine nucleotide exchange factors), GAP's (GTPase activating proteins) |
|
|
Term
| G-proteins are (protein-linked, lipid-linked, covalently bound) to G-protein receptors |
|
Definition
|
|
Term
| what are the 4 phases of the cell cycle (cell division)? |
|
Definition
M phase: mitosis and cytokinesis
Interphase: time between M phases
S phase: synthesis of DNA
G phases: Gap phases (there are 3 G1, G2 and G0 - G1 and G2 occur in normal cell division but G0 only occurs when cell division is not favorable) |
|
|
Term
| what are cyklin-dependent kinases (Cdks)? |
|
Definition
| kinases involved in the control of cell cycle events |
|
|
Term
| what is the allosteric regulator protein for Cdks? |
|
Definition
|
|
Term
| when are M-Cdk levels highest? |
|
Definition
| during mitosis (low during interphase) |
|
|
Term
| how does M-Cdk indirectly activate itself (positive feedback)? |
|
Definition
| by activating an activating phosphatase (removes an inhibiting phosphate) and inhibiting an inhibiting kinase (adds inhibitory phosphate) |
|
|
Term
| how does M-Cdk participate in a negative feedback pathway? |
|
Definition
| by initiating a series of events that ultimately leads to the activation of ubiquitinating enzymes which add ubiquitin to the M-Cdks and mark them for destruction by a proteosome |
|
|
Term
| what is the role of S-Cdks? |
|
Definition
| to start DNA replication by phosphorylating an intiator protein at an ORI which leads to replication fork formation and thus DNA replication |
|
|
Term
| how do M-Cdks aid in the process of mitosis? |
|
Definition
| they activate lamins (nuclear "cytoskeleton" component) which leads to nuclear envelope breakdown, condensins (proteins involved in chromatin packing)which leads to chromosomal condensation and microtubules (cytoskeleton component)which leads to spindle formation |
|
|
Term
| what is the normal function of retinoblastoma? what is it controlled by? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| G1-Cdks are activated by _________ and prepare the cell for cell division by increasing the substrates necessary for _____________ and ___________ |
|
Definition
| mitogens, replication, S-phase |
|
|
Term
| what is p53 and how does it act as a cell cycle checkpoint? |
|
Definition
| it is a protein that activates transcription of Cdk inhibitor. if cell is normal, p53 is rapidly degraded by ubiquiton but if there is a break in the dsDNA, a kinase is activated which phosphorylates p53 and stops it from being ubiquinated. this leads to an increase in Cdk inhibitors and NO replication! checkpoint for internal environment of cell |
|
|
Term
| at the ____ checkpoint the cell monitors whether DNA replication is complete and error free and at the ____ checkpoint the initiation of chromosome separation is regulated by proper attachment of chromosomes to the mitotic spindle |
|
Definition
|
|
Term
| compare and contrast necrosis and apoptosis |
|
Definition
both are types of cell death
necrosis is cell death in response to an acute injury. in this type of cell death the cell swells and bursts spilling cellular contents into the extracellular space and causing inflammation (immune response)
apoptosis is programmed cell death in response to DNA damage or a lack of survival signals. in this type the cell shrinks and blebs (forms "vesicles") and an inner leaflet lipid flips out outer leaflet, sign to immune cells to endocytose |
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|
Term
| __________ are the family of enzymes that catalyze the apoptotic breakdown of proteins |
|
Definition
|
|
Term
| how are caspases activated? |
|
Definition
| by being cleaved into three parts: the prodomain which has no activity, and a small and large subunit which rearrange to form an active caspase |
|
|
Term
| what are the two classes of apoptotic caspases? |
|
Definition
1. initiator caspases: start signal cascade
2. executioner caspases: activated by initiator caspases, cleave cellular targets -> apoptosis |
|
|
Term
| true or false: caspases play a role in amplification |
|
Definition
|
|
Term
| what are the main targets of executioner caspases? |
|
Definition
| other caspases, proteins that regulate DNases, DNA repair enzymes, cytoskeltal proteins, nuclear lamins |
|
|
Term
| in what two ways are initiator caspases activated? |
|
Definition
| by internal signals such as sever DNA damage, or the binding of an external "death" signal |
|
|
Term
| ________________________ promote the clustering of caspases which results in ________________ and ________________ |
|
Definition
| procaspase adaptor proteins, caspase cleavage, activation |
|
|
Term
| the process of cancerous cells migrating from a primary malignant tumor to other tissues (via the bloodstream) and forming seconday tumors is called ________________ |
|
Definition
|
|
Term
| a ___________ tumor is the result of uncontrolled, localized cell growth and a ___________ tumor is the result of uncontrolled, mobile cell growth |
|
Definition
|
|
Term
| what are some of the key characteristic of cancer cells? |
|
Definition
1. genetic instability-incorrect numbers of chromosomes (aneuploidy)
2. ignore extracellular death and growth limiting signals
3. no reliance on extracellular growth signals
4. immortal
5. invasive
6. have sustained angiogenesis (ability to induce blood vessel formation)
7. motile |
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|
Term
| a _______________ is a normal functioning gene that becomes a __________________ when it becomes constitutively active |
|
Definition
|
|
Term
| true or false: oncogenes are recessive, therefore only homozygotes will develop cancer |
|
Definition
| false. they are dominant so even one coy of the gene (heterozygote) will lead to tumor formation |
|
|
Term
| ________ is a proto-oncogene and _____ is a tumor suppressor gene |
|
Definition
|
|
Term
| in order for a tumor to form as the result of mutant tumor suppressor genes there must be ______ mutant copies |
|
Definition
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