cellular communication – Flashcards
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| if a signaling molecule is bound to the surface of a cell it induces ____ which is important in development, immune reactions, synaptic signaling and neurons/neuromuscular junctions |
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| contact-dependent signaling |
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| what is autocrine signaling? |
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| if the same cell can respond to the signal it produces |
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| what is paracrine signaling? |
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| if the cell's signal acts on nearby cells |
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| what is endocrine signaling? |
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| long distance communication between cells involving hormones traversing the bloodstream |
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| where does signal reception take place on the target cell? |
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| usually at transmembrane proteins, but in the case of small lipid soluble molecules, they can be intracellular |
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| intracellular pathways consist of cascades of intracellular signaling proteins, distributing the signal to the targets -> effector protein, what are examples of this protein? |
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| gene regulatory proteins, ion channels, components of the metabolic pathway, and parts of the cellular cytoskeleton |
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| how do ion channel coupled receptors function? |
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| a signaling molecule binds to the protein and the channel opens, allowing passage of ions |
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| how do G protein coupled receptors act? |
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| they act indirectly by regulating the activity of another membrane associated protein, (such as adenylate cyclase) |
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| how do enzymatic coupled receptors work? |
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| the ligand binding site is located on the outside of the cell, and the catalytic domain is intracellular. sometimes a separate enzyme can be associated with the intracellular portion of the receptor |
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| what are the 3 small intracellular signaling molecules we should know and their solubilities? |
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| cAMP and Ca+ are water soluble and diffuse in the cytosol. diacylglycerol, (DAG) is lipid soluble and diffuses in the plane of the plasma membrane |
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| what do large signaling molecules do? |
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| help generate small signaling molecules or activate the next signaling or effector molecule |
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| what is the acronym to remember the first four mechanisms for large signaling molecule action? |
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| STAR - Scaffold, (bring signaling proteins together for more efficient/fast interaction), Transform, (or transduce signal forms), Amplify, Relay, (from one signal to the next) |
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| what is the acronym to remember the second four mechanisms of large signaling molecules? |
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| SAMI - Spread, (from one pathway to another - "branches"), Anchor, (keep the molecule where its needed), Modulate, (the activity of other signaling proteins), Integrate, (2 or more signaling cascades, coincidence detector) |
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| what does a protein kinase do? what are 2 important kinds? |
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| covalently adds a phosphate group, (usually from ATP). serine/threonine or tyrosine kinase |
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| what does a protien phosphatase do? |
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| removes a phosphate group. there are also serine/threonine or tyrosine phosphotases |
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| how do GTP binding proteins function? |
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| when GTP is bound, they are "on". when GDP is bound, they are "off". also, when they are on, they can turn themselves off |
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| what kinds of GTP binding proteins are there? |
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| large, (part of G protein coupled receptors), and small, which help relay signals from a variety of other receptors |
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| how do GAPs and GEFs regulate GTP-binding proteins? |
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| when "on" or in the GTP bound state, GTPase activating proteins, (GAPs) increase the rate of hydrolysis, (by GTPase). when in the "off" state, Gunanine nucleotide exchange factors (GEFs) can activate GTP binding proteins, promoting formation of GTP |
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| what is one way that parallel pathways can be integrated? how does this process work in a more permanent manner? |
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| scaffolding, the scaffold holds the intracellular signaling proteins inline under the receptor, so that when the signal comes down, they are all activated in a line |
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| how can scaffolding occur in a more temporary fashion? |
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| a receptor's intracellular domain extends into the cytoplasm, it is phosphorylated, (often auto-phosphorylated), and the intracellular signaling proteins line up on it the signal is distributed to all at the same time |
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| what 2 signaling molecules bind phosphorylated tyrosines? |
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| Src homology 2 (SH2) domains, and phosphotyrosine binding domains, (PTB) |
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| what signaling molecule binds prolines in protein to protein interactions? |
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| Src homology 3 (SH3) domains |
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| what signaling molecule binds phosphorylated lipids, (phosphoinositides)? |
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| Pleckstrin homology (PH) domains |
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| if the insulin receptor has intrinsic kinase activity what process does it participate in? |
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| autophosphorylation |
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| when a ligand binds to a GPCR, what happens? |
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| it undergoes a conformational change, enabling it to interact with a G protein, (sometimes it is already associated/sometimes not). the G protein then couples the receptor to the enzymes or ion channels. |
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| what 3 subunits make up G proteins? what functions do they serve? |
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| alpha, beta, gamma. the alpha has GDP bound to it in the inactive state, and when the GPCR is activated it acts like a GEF. the alpha subunit is a GTPase, which can then inactivate it. the beta has enzymatic regulatory function, and the gamma - ? |
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| what G protein produces cAMP, a small intracellular signaling molecule? what destroys it? |
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| adenylate cyclase, and cAMP phosphodiesterase, respectively |
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| what do Gs and Gi do? |
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| they are 2 kinds of regulatory G proteins that stimulate and inhibit adenylate cyclase |
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| how does cAMP regulate its cAMP-dependent protein kinase, (PKA)? |
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| cAMP binds to PKA's regulatory subunits, which upon binding dissociate from the catalytic subunits, allowing them to do their work |
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| after cAMP binds to PKA, causing dissociation from the regulatory subunits, where do the catalytic subunits go? |
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| the activated PKA subunit goes to the CREB binding protein in the nucleus, which covers the cAMP response element, (it subsequently detaches),part of the DNA |
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| how are IP3 and DAG released by a G protein pathway? |
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| some G proteins activate an inositol phospholipid signaling pathway. Phospholipase C beta hydrolyzes phosphatidylinositol 4,5 bis-phosphate, (PIP2), into diacylglycerol, (DAG) and inositol 1,4,5-triphosphate, (IP3) |
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| once released by phosphatidylinositol 4,5 bis-phosphate, (PIP2) mediated hydrolysis, instigated by a G protein, what does inositol 1,4,5-triphosphate do? |
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| IP3 is a water soluble molecule that acts on the ER to open IP3-gated Ca+ release channels, which is followed by another plasma membrane Ca+ channel opening, resulting in a rapid rise in intracellular Ca+ concentration. |
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| once released by phosphatidylinositol 4,5 bis-phosphate, (PIP2) mediated hydrolysis, instigated by a G protein, what does diacylglycerol do? |
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| DAG remains embedded in the plasma membrane, which can be cleaved to release arachidonic acid, further metabolized to create prostaglandins, (an eicosanoid), or it can activate a Ca+ dependent protien kinase C, (family of serine/threonine kinases) |
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| when Ca+ is released either via IP3 or DAG, what is one thing it can do in the cell? |
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| Ca+ complexes with calmodulin, which undergoes a confirmational change and activates a calmodulin-dependent kinase, which among other things controls transcription |
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| do GPCRs and enzyme coupled receptors often activate the same signaling pathways? |
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| yes |
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| what kinds of enzyme coupled receptors are included in Receptor Tyrosine Kinases? |
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| many related to growth factor, including insulin |
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| what do the phosphorylated tyrosines on RTKs function as? |
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| high affinity docking sites, which sometimes may increase the kinase activity of the receptor itself |
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| RTKs can activate ras, how is this connection regulated? |
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| by GAPs binding to RTK via SH2, and GEFs binding to Grb2, (adaptor protein), which binds to RTK. ras can also be activated b Ca+ and DAG |
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| what does ras do when activated? |
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| ras activates the MAP, (mitogen activated protein), cascade, (MAPKKK->MAPKK->MAPK) = the end result is cell division, (cyclins activated) |
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| what is a janus kinase? |
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| a cytoplasmic tyrosine kinase, which when activated by a receptor, phosphorylates and activates gene regulatory proteins called STATs, (signal transducers and activators of transcription), (very direct) |
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| what does phosphoinositide 3 kinase, (an RTK), do? |
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| adds a phosphate on the 3rd carbon of phosphoinositides |
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| what is the most important phosphoinositide acted on by phosphoinositide 3 kinase? |
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| PI(3,4,5)P3 b/c it is a docking site for intracellular binding proteins, particularly the serine/threonine protein kinase Akt |
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| what does Akt,(protein kinase B) do? |
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| Akt binds with Phosphoinositide dependent protein kinase 1, which activates it, and then regulation of cellular proteins including those that regulate apoptosis is possible |
