Chapter 10: Cell Signaling Flashcards
The basics of cell signaling (behavior of signaling molecules)
- Cells in multi cell molecules no operate independently, each has a specific function to carry out for the physiology of the organism.
- Extra-cellular signal moles released by signaling cells that bind receptor proteins on target cells and tell them to perform a function
Types of signaling molecules, their polarity, and how differences in polarity affect their passage through the body
Types of signals: polar: soluble in blood cant pass through mem. non polar transported by carrier proteins can pass through mem.
• Proteins/Peptides (Ex. Insulin) – polar
• Modified amino acids (Ex. Epinephrine) – polar
• Modified fatty acids (Ex. Prostaglandins) - nonpolar
• Steroids (Ex. Testosterone, Estrogen) – nonpolar
• Dissolved gases (ex. Nitric oxide)
• Differentiate between the five types of signaling and the function of particular components in each pathway
- Endocrine (epi from adrenal glands binds muscle cells)
• Long range signaling by hormones produced by endocrine cells
• Hormone from distant gland binds to target cell - Paracrine (inflammatory responses)
• A cell signals adjacent cell
• local mediators, diffuse through extracellular fluid - Autocrine ( tumor cells signal their own proliferation and survival)
• cell releases a factor that binds back to same cell - Synaptic (Neuronal)
• Neuronal signaling can happen over big distances -> propagation of ap
• signal component involves nt that signal across synapse - Contact Dependent (cell specialization during development)
• Covers short distances
• NO secreted molecules
• Uses mem-bound signal molecules to elicit response in target cell
- Differentiate between the classes of signaling molecules
2. how cells selectively respond to these signals (gene expression vs existing proteins)
1.
• Large/hydrophilic = bind cell surface receptors which relay a signal to the inside of the cell
• Small/hydrophobic = pass through membrane and bind receptor molecule inside the cell
2.
• Responses leading -> gene expression, often slower: mins-hrs (as the cell has wait for transcription and translation; growth hormones signaling cell division)
• Responses leading -> alteration/modification of existing proteins, often fast: secs-mins (acetylcholine signaling muscle cell contraction)
• Differentiate between steroid and non-steroid signaling molecules
- Steroid signals can pass through the mem. and into bloodstream; only synthesized when needed
- Non-steroid hormones are secreted through exocytosis; can be produced, held in cell until needed, then released upon stimulus
• Details of the steroid hormone pathway and how steroids elicit a signaling response (include all components involved in the process)
- Steroid hormones pass through plasma membrane
- Binds to steroid hormone receptor in cytoplasm activating it
- Binding together of steroid/receptor allows it to be imported into the nucleus where it can induce transcription of specific genes into mRNA, mRNA translated into specific protein
The nature of cell surface receptors and the three major classes they fall into
- Cell surface receptors carry out primary step of signal transduction when they bind their signaling molecule and relay the signal inside cell.
- ION CHANNEL-COUPLED RECEPTORS – involved with rapid synaptic signaling
- ENZYME-COUPLED RECEPTORS – either are enzymes or activate enzymes
- G-PROTEIN COUPLED RECEPTORS (GPCRs) – signal transduction occurs through the activation of a G-protein (receptor activates G-protein then Gprotein activates a membrane bound enzyme/channel)
The nature of signal transduction pathways and the mechanism of intracellular signaling molecules, second messengers and effector proteins
- Signal-bound cell surface receptors relay the signal in the cell to intracellular signaling molecules
- Some of these are ions and small non-protein molecules, called 2nd messengers (cell surface receptor is 1st)
- 2nd -> diffusion to activate proteins & enzymes involved in sigaling pathway
- Some 2nd messengers are cytosolic like Ca2+ and cyclic AMP
- Others are membrane bound like diacylglycerol (DAG)
- Effector proteins usually at end of pathway. modified in way that produces cell response
Examples of second messengers and where they function/exist
- Second messengers: some of these are ions or small non protein molecules, they spread by diffusion to activate proteins and enzymes involved in signaling pathway.
Cytosolic: Ca2+ and cyclic AMP
Mem bound: diacylglycerol
• The nature of molecular switches and the two major types
• Some icsp called molecular switches because they can be turned on and off
• Remember, kinases are enzymes that add phosphate groups to other enzymes often activating them
• Phosphatases are enzymes that remove phosphate groups from enzymes often inactivating them
• The largest group of molecular switches involve enzymes that are turned on and off by the addition/removal of a phosphate
- enzymes called gtp binding proteins
The mechanism of different types of protein kinases and how they function in phosphorylation cascades
- Kinases can activate other kinases and produce a phosphorylation cascade = amplification
- 2 classes of protein kinases:
- serine/threonine kinases
- Put a PO4 on Ser/Thr
- tyrosine kinases
- Put a PO4 on Tyr
• Describe the detailed mechanism of GTP-binding proteins and how they work to elicit a cell signal
- The second most common molecular switches are enzymes called GTP-binding proteins
- When bound to GTP, the enzyme is active; when bound to GDP, the enzyme is inactive
- These enzymes have GTP-hydrolyzing activity - they can inactivate themselves by hydrolyzing the GTP bound to them
Differences in signaling between monomeric vs trimeric GTP-binding proteins
- Monomeric GTP-binding proteins relay signals from many classes of receptors
- Trimeric GTP-binding proteins relay signals specifically from Gpcr
The detailed mechanism of how GEFs and GAPs are involved in controlling GTPases and signaling
• While GTP-binding proteins have intrinsic GTPase activity, most of the time, regulatory proteins are actually controlling it
Regulation of GTP-binding proteins involve two proteins:
• GEF (guanine exchange factor) = stimulates the release of GDP so GTP can bind = active
• GAP (guanine activating protein) = stimulates hydrolysis of GTP = inactive
The detailed structure of GPCRs and the generic step-by-step mechanism of how they relay a signal
- Each GPCR = capable of binding diff. ligand and relaying signal to specific G-protein in cell
- all =single pp which fold into a 7-pass mem. protein
- GPCRs activate trimeric G-proteins; the individual subunits of the trimer include α, β, y, but only α and γ are tethered to mem.
- The α = GTPase , in inactive state a= GDP
- When bound to signaling molecule, the GPCR undergoes a cc and acts as GEF causing the α to release GDP
- This allows it to bind GTP = activated
- Once activated, α dissociates from both the GPCR and β/γ
- Dissociation of β/γ from α activates it too, so now we have active α and active β/γ
- Each regulate downstream signaling molecules; signaling lasts for as long as α is bound to GTP
