2. Smooth muscle dialates in response to the peripheral NS relesasing neurotransmitter acetylcholine
3. Acetylcholine receptor is on endothelial cell, and Ach binds to it. That endothelial cell synthesizes NO which diffuses across membrane into muscle which is bound by NO receptor, which then allows smooth muscle relaxation.
13. Binds GTP and GDP (reason why it’s called a G protein)
14. Active when bound to GTP, but GTP will only be in GTP state for so long – androgenous hydrolase activity, hydrolysis takes place and GDP bound state as Pi is removed.
19. The alpha subunit always binds GTP, but when there is separation and diffusion through the membrane it depends on the type of HG-protein to which protein the alpha or beta/gamma subunit will be doing the next action
20. In active state, beta/gamma subunit and alpha subunit separate and the beta and gamma act as a dimer
38. Binding to the receptor induces conformational change on receptor that allows interaction with heterotrimeric G protein
39. Interaction of the heterotrimeric G protein activates G protein allowing alpha subunit to bind GTP
40. Alpha subunit binding to GTP causes a release of the alpha unit from beta/gamma subunit
41. The beta/gamma subunit activates an enzyme near the plasma membrane of cell, and allows that enzyme to cleave phospholipids in the membrane
42. PIP2 – Phosphoinositol bisphospahte, main component of phospholipid membrane, is cleaved by an enzyme that breaks it into two important signaling molecules
48. Receptor opens up and allows Ca2+ channel to open and allow it into the cytosol, so intracellular calcium levels increase
49. The Ca2+ is immediately bound up by the calcium binding proteins, in this case called calmodulin – 4 Ca2+ opens up calmodulin structure so it can interact with other proteins
50. One result of this is the activation of NO synthase – so now we have increased levels of active NO synthase, and the NO synthase will convert arginine to NO.
51. NOTE:: All of these steps occur within the cytoplasm of the endothelial cell after Ach binds to the receptor in order to just make NO, which can diffuse across the membrane and lead to relaxation.
53. When NO Diffuses across membrane to smooth muscle cell, it also binds to receptor for NO and then from there, the signaling continues to allow the smooth muscle to relax, this is not a direct effect
54. Binding of NO to receptor activates an enzyme called guananyl cyclase, which converts GTP to cGMP, by removing two Pi.
56. in this case, 2 bind and activate protein kinase G by binding it
57. many kinases have specific conformation for catalytic sites for kinase functions (phosphorylation of targets) until regulatory sites are bound and in this case, the reg. sites are bound by cGMP, and when they are bound, changes confo. Of proteins to open to catalytic sites are open and can recognize targets.
60. When inactive, Ca2+ cannot, extracellular Ca2+ channels in the plasma membrane cannot open when phosphorylated, come into EXC space form smooth muscle. Induces relaxaition, Ca2+ is required for muscle contraction, so with low Ca2+ levels, smooth muscle is forced to relax. Muscle relaxation is caused by phosphorylation of Ca2+ channel.
61. Eventually will be dephosphorylated by phosphatases and the smooth muscle can contract
62. As long as protein kinase G is active, you have relaxation of smooth muscle.
94. Increased levels of cortisol results from too much ACTH production or overactive cortisol production – Cushing Syndrome – (10-15 per million people)
95. Difficult to regulate because trying to eliminate cortisol is more detrimental than not having enough
98. Caused as a result of tuberculosis or fungal infection
99. Immune system tries to deal with either of these and creates granulomas – sites where healthy cells are killed in the process of trying to deal with the infection
100. Reduces size and function of adrenal cortex. Replaces with immune cell masses
123. Two very important components of signaling part of the intracellular signaling protein pathways are molecular switches, called as such because they work just like a light switch.
145. Interact with heterotrimeric G proteins, the alpha/beta/gamma subunit proteins and NOT the small G proteins that are single subunit proteins that bind GTP or GDP.
164. Exposed after ligand binding (confo change) that will interact with heterotrimeric g protein in plasma membrane
165. Sits in an inactive state in the membrane where the alpha subunit is bound to GDP
166. Difference between heterotrimeric g proteins and small g proteins is that the heterotrimeric g proteins are linked to the membrane and small g proteins are not – they are solube proteins in the cytoplasm.
168. when loop is exposed on receptor, the heterotrimeric g protein moves as a unit and binds to loop
169. alpha subunit underges a conformational change exposing a site for GTP binding (GEFs come in)
170. GTP when bound, leads to activation of heterotrimeric g protein, which separates the alpha beta/gamma subunits and the two separate subunits (alpha and beta/gamma) are activated
173. Heterotrimeric G proteins – trimeric protein with three subunits that make a single functional proteins where alpha subunit interacts with GTP and GDP.
![3.17.2010 – Cell Signaling Continued<br />,[object Object]](https://image.slidesharecdn.com/3-17-2010-100503153840-phpapp02/85/3172010-1-320.jpg)
