Cell Signaling II Flashcards
Describe the activation of phospholipase C-
ß
Gq activates PLC
Indicate which bond in PI(4,5)P2 is hydrolyzed by phospholipase C-ß and name the resulting products
The bond that connects the two phosphate groups to the membrane is hydrolyzed.
This results in the production of diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3)
Discuss the role of diacylglycerol in signal transduction.
DAG activates PKC, which can phosphorylate ser + thr residues
Compare the concentration of Ca2+
in the cytosol to that in the endoplasmic
reticulum and outside the cell, and explain how this difference is maintained.
There is a greater concentration of Ca2+ in the ER and outside the cell than in the cytoplasm. This is maintained by certain channels that keep Ca out, such as the Na-driven Ca exchanger and the Ca pump, as well as Ca pumps in the ER and mitochondrial membranes.
Describe the role of inositol trisphosphate (IP
3) in signal transduction.
IP3 releases Ca from the ER, which opens more Ca channels. The increase in cytosolic Ca can have multiple effects. Eventually, channels close by feedback inhibition, terminating the spike of signal. The frequency of these spikes, rather than the amplitude, increases with more signal. Ca binds calmodulin, which can now bind many enzymes and membrane transport proteins and alter their activity.
Using vasopressin-induced Ca2+ oscillations n a liver cell as an example, describe
the effect of the hormone concentration on oscillatory frequency.
Hormone concentration is directly related to the frequency of Ca2+ oscillations in a liver cell.
Describe the structure of calmodulin, including the number and location of the Ca2+ binding sites.
Calmodulin is an alpha helix with four Ca binding sites.
Discuss how the binding of Ca2+ to calmodulin affects its structure and function.
When at least two of calmodulin’s binding sites are filled, the protein is capable of wrapping around enzymes and membrane transport proteins to alter their activity.
Indicate how Ca2+/calmodulin activates CaM-kinase II, and how CaM kinase remains active even after cellular Ca2+ has decreased.
When Ca2+-calmodulin binds CaM-kinase II, it partially activates its kinase activity. The CaM kinase then phosphorylates itself, resulting in complete activation that persists even after Ca2+ decreases and calmodulin dissociates from it.
How is CaM-kinase II activity turned off?
A phosphatase cleaves the phosphate bond, deactivating the kinase
Discuss how the frequency of Ca2+ oscillations can affect CaM-kinase II activity.
The higher the frequency of Ca oscillations, the easier it is for CaM-kinase II to be phosphorylated and the less time for a phosphatase to dephosphorylate the kinase.
What does cGMP activate, and what does this molecule do?
It activates Protein Kinase G, which phosphorylates Ser/Thr residues
Discuss how activation of the inositol phospholipid pathway can have different effects in different cell types.
Different cell types may have different molecules available for phosphorylation. This would, then, result in a different cell response to the same signaling pathway.
Identify the major signal transduction mechanisms for the different adrenergic receptor subtypes.
Alpha 1’s use Gq – phospholipase C, DAG+PKC, IP3+ca-calmodulin
Alpha 2’s use Gi, Go (not mentioned) – inhibitory, adenylyl cylcase
Beta’s use Gs – stimulatory, adenylyl cyclase
Describe how bradykinin can stimulate the formation of NO in endothelial cells?
Bradykinin binds a GPCR associated with Gq. Gq then activates PLC, which breaks down the PIP into DAG and IP3. IP3 releases calcium from the ER, and the calcium-calmodulin complex binds the nitric oxide synthase (NOS). When arginine binds the enzyme, NO is generated.
