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Biochem Ch. 13
Signal Transduction Pathways
| Question | Answer |
|---|---|
| __________ ___________ is an important capability in all life forms. It allows an organism to sense its environment and formulate the proper biochemical resposne | signal transduction |
| Signal-transduction pathways can be viewed as a molecular _______ | circuit |
| Signal-Transduction Components: (1) ________ of a primary message as a response to a physiological circumstance | release |
| Signal-Transduction Components: (2) __________ of the primary message by a receptor, usually an integral membrane protein | Reception |
| Signal-Transduction Components: (3) _______ the detection of the primary message to the cell interior by the generation of an intracellular SECOND message. | Relay |
| Signal-Transduction Components: (4) ____________ of effector molecules by the second messenger that result in a physiological response. | Activation |
| Signal-Transduction Components: (5) ___________ of the signal cascade. | Termination |
| Signal-Transduction Components: _________ pathways regulate the entire system | feedback |
| There are _#_ major classes of membrane receptors | three |
| Three Classes of Membrane Receptors: (1) _____ ___________ receptors associated with heterotrimeric G-proteins | seven transmembrane |
| Three Classes of Membrane Receptors: (2) _________ _________ receptors that recruit protein kinases | dimeric membrane receptors |
| Three Classes of Membrane Receptors: (2) _________ _________ receptors that ARE protein kinases | dimeric protein receptors |
| The seven-transmembrane-helix (7TM) receptors mediate a host of biological functions by responding to a variety of signal molecules, or __________ | ligands |
| 7TM Receptors: What does the binding of a ligand outside the cell induce? | a structural change in the 7TM receptor that can be detected inside the cell |
| 7TM Receptors: Ligand binding to the 7TM receptors leads to what? | activation of GTP-binding proteins (G protein) |
| 7TM Receptors: upon activation by the receptor, the α subunit dissociates from the βγ dimer and exchanges ___ for ___. | GDP for GTP. |
| 7TM Receptors: The GTP bound α-subunit then does what? | transmits the signal to other cellular components. |
| 7TM Receptors: Because 7TM receptors are always associated with G proteins, they are often called what? | G Protein Coupled Receptors (GPCR). |
| 7TM Receptors: β-Adrenergic Receptor binds epinephrine, activating the G protein. In this example, what does the activated G protein stimulate? | it stimulates the intergral membrane enzyme, Adenylate Cyclase |
| 7TM Receptors: Activation of the cyclase leads to the synthesis of the second message. What is the 2nd message? | cyclic Adenosine Monophosphate (cAMP). |
| Cyclic AMP stimulates phosphorylation of many target proteins by activating what? | protein kinase A (PKA) |
| Kinase | enzyme that phosphorylates a substrate at the expense of ATP |
| PKA consists of 2 _________ subunits and 2 ___________ subunits | regulatory (R), catalytic (C) |
| In the absence of cAMP, the R2C2 complex of PKA is catalytically _________ | inactive |
| Where does cAMP bind? How does the binding of cAMP activate the PKA complex? | Binding of cAMP by the regulatory subunits dissociates these subunits from the complex resulting in activation of the 2 catalytic subunits. |
| The activated catalytic subunits continue the Epinephrine Signal Transduction Pathway by doing what? | phosphorylating protein targets that alter physiological functions of the cell. |
| The cAMP cascade is turned off by cAMP _______________, an enzyme that converts cAMP into AMP, which does not activate PKA | phosphodiesterase |
| G proteins spontaneously reset themselves through what? | GTP Hydrolysis |
| Gα subunits have intrinsic _____ activity that hydrolyzes bound GTP to GDP + Pi. The Gα bound to GDP spontaneously reassociates with the βγ subunits terminating the activity of the G protein. | GTPase |
| Besides GTP Hydrolysis, what is another way the epinephrine-initiated pathway is shut down? | cAMP phosphodiesterase converts cAMP to AMP which does not activate PKA |
| Signal termination: signal transduction by the 7TM receptor is halted, in part, by what? | dissociation of the signal molecule from the receptor |
| cAMP is not the only second messenger employed by 7TM receptors and G proteins. We now look at another second-messenger cascade used by many hormones to evoke a variety of responses. the __________________ cascade. | phosphoinositide cascade |
| What does the phosphoinositide cascade do? | like adenylate cyclase cascade, it converts extracellular signals into intracellular ones. |
| The intracellular messengers formed by activation of the phosphoinositude pathway arise from hydrolysis of a phospholipid, _____ | PIP2 (phosphatidylinositol Biphosphate) |
| phosphoinositide cascade: Binding of a hormone to its 7TM receptor leads to the activation of _____________ __, which cleaves PIP2 | phospholipase C |
| phosphoinositide cascade: The G protein that activates phospholipase C is called what? | Gαq |
| phosphoinositide cascade: The Gαq protein activates phospholipase C. The activated enzyme then cleaves PIP2 and produces two messengers: | IP3 and DAG |
| IP3 is a soluble molecule that can _________ from the membrane, DAG stays in the membrane | diffuse |
| What does IP3 do? | binds IP3 gated channel in the ER, allowing an influx of Ca2+ ions into the cytoplasm (Ca2+ regulates a host of cellular functions) |
| What does DAG do? | in conjunction with Ca2+, it activates PKC (a serine/threonine kinase) |
| The 7TM receptors initiate signal-transduction pathways through changes in ___________ structure that are induced by ligand binding | tertiary |
| For another class of receptors, ligand binding leads to changes in ________________ structures -specifically the formation of receptor _______. | quaternary, dimers |
| A receptor that dimerizes when ligand is bound contains an extracellular domain, a transmembrane region, and a cytoplasmic domain that either binds a protein kinase or is a protein kinase. What is a good example of this type of receptor? | the growth-hormone receptor (also the epidermal growth factor EGF) |
| Explain how the binding of a growth hormone leads to receptor dimers | a single growth-hormone molecule interacts with the extracellular domains of TWO receptors. Binding the two receptors leads to the formation of a receptor dimer |
| Dimerization of the extracellular domains of the two receptors brings together the ____________ domain as well | intracellular |
| Associated with each intracellular domain is a molecule of tyrosine protein kinase, termed ______ in an unactivated form | JAK2 |
| How does dimerization of growth-hormone receptors activate the JAK2 proteins associated with each intracellular domain? | dimerization brings together the JAK2 proteins. Each kinase phosphorylates its partners (cross-phosphorylation) resulting in the activation of the kinases |
| The activated JAK2 kinases then phosphorylate other targets, including a regulator of gene expression called signal transducer and activator of transcription 5 (STAT5). What does STAT5 do? | STAT5 further propagates the signal by altering gene expression |
| receptor tyrosine kinases, such as the epidermal-growth factor (EGF) receptor and the insulin receptor have _______________ domains that ARE kinases | intracellular |
| A key component of the EGF pathway is the protein ____ | Ras |
| Ras is a member of the family of signal proteins called small G proteins or small _________. | GTPases |
| Ras is similar to the Gα protein. how so? | Ras is active when bound to GTP and inactive when bound to GDP. (Ras also has intrinsic GTPase activity to terminate the signal and return system to inactive state) |
| Other proteins function to ___________ the GTPase activity of Ras | modulate |
| when receptor tyrosine kinases dimerize and are activated, they are cross-phosphorylated. What doe the phosphorylated tryosines in active receptor tyrosine kinases do? | they serve as docking sites for signaling proteins and permit further propagation of the signal |
| _______ is amond the principal hormones the regulate metabolism | insulin |
| The polypeptide hormone, insulin, is secreted when the blood is rich in __________. | glucose (Insulin is the biochemical signal for the fed state.) |
| Explain the structure of insulin | two polypeptide chains linked by disulfide bonds |
| What kind of receptor is the insulin receptor? | a tyrosine kinase |
| How does the insulin receptor differ from other tyrosine kinases? | the insulin receptor exists as a dimer even in the absence of insulin |
| Receptor dimers form on insulin bindind leading to cross-phosphorlyation and activation of the kinase domains. What do these activated kinases do? | phosphorylates additional sites within the receptor. these phosphorylated sites act as docking sites for other substrates |
| The activated kinase of the insulin receptor phosphorylates insulin-receptor substrates (IRS). What are these phosphorylated IRSs? | adaptor proteins that convey the insulin signal |
| Phosphoinositide-3 kinase binds to the IRSs and then phosphorylates ____to form ____ | PIP2 to form PIP3 |
| What does PIP3 activate? | PIP3-dependent kinase |
| When PIP3-dependent Kinase (PDK1) is activated, what does it do? | phosphorylates and activates the kinase AKT. |
| What does AKT do when it is activated? | phosphorylates glucose transporter (GLUT4) INCREASING glucose uptake by the cells as well a enzymes that convert glucose into glycogen. |
| How can a small increase in insulin concentration produce such a robust intracellular response? | The signal is amplified at several stages along the pathway (enzymatic reaction = amplification) |
| Insulin signaling is terminated by the action of ____________ | phosphatases |
| how do phosphatases terminate the insulin signaling? | they remove phosphates from activated proteins in the insulin signal transduction pathway, terminating the insulin signal |
| Lipid phosphatases contribute to signal termination by converting ____ into ____ | PIP3 into PIP2 |
Created by:
cmccartney2