Define cell signaling and its main purpose
Process by which cells communicate with each other and their environment.
Purpose: Cell signaling changes cell behavior based on external or internal signals
External: Nutrients, oxygen, toxins, sensory cues
Internal: Hormones, nutrients, neurotransmitters, metabolites
Identify the main components of a signaling pathway
- Signaling cell
- produces signals such as hormones and neurotransmitters - Target cell
- has specific membrane receptor proteins that receive signals
List the three main types of signals and provide at least one example belonging to each signal class
- Autocrine (send signal to itself)
- Paracrine (send signal to nearby cells)
ex. Synaptic signaling:
- pre-synaptic cell sends signals in the form or neurotransmitter to post-synaptic cell - Endocrine (send signals to far cells via the circulatory system)
Ex. Hormonal signaling
- horomones produced by endocrine glands secrete into bloodstream and send to organ cells
List the basic steps in cell signaling, and the role that each steps plays in generating a cellular response
- Initiation
- receptor protein recognizes extracellular signal and generates new intracellular signal in response - Propagation
- 1:1 (signal protein ratio)
- relays signal and activates signalling protein inside cell (causes protein conformation change) - Amplification
- 1: many (signal protein ratio)
- makes signal stronger by allowing it to modify multiple intracellular proteins - Cellular response
- modifies effector proteins (changes function, structure, or identity ) - Termination
- ends cell signaling
Discuss how receptors influence the cellular response to a signal
- cell can only respond to signal if it expresses a receptor for that signal
- specific Receptors are expressed in certain types of cells (liver cells have different receptors than bone cells)
- cells may express different receptors at different stages in their development
Identify two main types of receptors
- Cell-surface receptors
- binds to large, hydrophiliic molecules
ex. ion-channel-coupled, G-protein-coupled, Enzyme-linked - Intracellular receptors
- binds to small hydrophobic molecules
ex. Steroic hormone receptors (enters nucuelus and can act as a transcription factor)
Multiple receptors can be made for a single signal
- results in different reactions and cellular changes
Describe differences between fast and slow cellular responses and give examples of each
Slow (HRS):
- signalling causes modification of TF and mediates transcription event
- creates new proteins
Fast:
- does not create new proteins and does not undergo transcription
- may either activate an inactivate protein in the cell or create a protein from existing free-floating mRNA / free-floating polypeptides
Describe how ion channel-coupled receptors help transmit information between neurons
change the permeability of plasma membrane to selected ions
- results in altered membrane potential and can lead to an eletrical current
Common in neurons
1. Pre-synaptic membrane releases neurotransmitters into synaptic cleft
2. neurotransmitters bind to neurotransmitter receptors on the post-synaptic membrane
3. Opens up the channel proteins to allow ions to enter the membrane and to either conduct or inhibit signal propagation
List 4 features of GPCRs and describe the sequence of events that occur once a signal binds to a GPCR
Features:
1. highly amenable to pharmacological manipulation (can be targeted by drugs)
2. 7 alpha-helices that traverse the membrane
3. Heterotrimeric protein: has 3 subunits (alpha, beta, and gamma)
4. alpha and gamma subunits tethered to cell membrane
Sequence of events:
1. Initiation
- GPCR binds to an external signal
- alpha associated with GTP and diassociated form beta and gamma
- Propagation
- alpha and beta-hamma subunits associate with different target enzymes
3a. Amplification
- enzymes are activated (undergoes phase change) by G proteins (adenylyl cyclase, phospholipase C)
- turns precursor subtstrate into small intracellular signal molecules (second messengers)
3b. Second amplification:
- activated adenylyl cyclase boost production of cyclic AMP.
- cyclic AMP activates PKA
Cellular response:
- PKA activates glycogen phosphrolyase in skeletal muscle via phosphorylation (rapid response)
- PKA causes transcriptional cahnges in neurons via activating TF (slow response)
- Termination: GTPase activity of alpha subunit sets timer for activity
- GTPase hydrolyzes GTP into GDP which causes alpha unit to dissociate from target enzyme and assoicate back with beta-gamma units. (return to original conformation)
- if alpha subunit is fast at hydroylizing, signal activity is short
Define second messenger, give at least 2 examples of second messengers
Definition:
small intracellular messenger molecules
Examples:
- Adenylyl cyclase produces cyclic AMP
- phospholipase C produces inositol triphosphate and diacylglycerol
- iositol triphosphate produces cytosolic Ca 2+
Identify multiple steps in the GPCR-mediated intracellular signaling cascade where the signal is amplified
3a. Amplification
- enzymes are activated (undergoes phase change) by G proteins (adenylyl cyclase, phospholipase C)
- turns precursor subtstrate into small intracellular signal molecules (second messengers)
3b. Second amplification:
- activated adenylyl cyclase boost production of cyclic AMP.
- cyclic AMP activates PKA
Identify 2 features of an enzyme-linked receptor
Features:
1. have enzymatic activity / directly couples with an enzyme
2. has a single transmembrane pass alpha helix
3. can mediate fast and slow changes in cell behaviour
4. can be activated by signals such as hormones and growth factors
Describe the series of steps after a cell receives a signal that would bind an RTK
- Initiation;
Receptor tyrosine kinases (RTKs) dimerize upon ligand binding
- induces RTK activity (autophosphorylation other half of dimer) - Propagation:
- activated receptors recruit proteins
(phosphorylated tyrosines serves as docking site for intercellular signaling protein)
3a. Amplifcation (activate Ras)
- receptor-assoicated proteins amplify signal by modifiying and phorphylating other proteins
Example:
- adaptor protein binds to phosphotyrosine and recruits a Ras-Guanine exchange factor
- Ras_GEF induces a change in an inactive Ras protein by swapping its bound GDP with a GTP (activates Ras protein)
- Ras protien sends signal
3b. Amplification (activate MAP-kinase)
- activated Ras protein activates three-kinase signaling module
ex
MAP kinase kinase kinase is phosphorylated by Ras protein and in turn phosphorlates MAP kinase kianse which phophorylates MAP kinase
- Cellular response:
MAP kinase phosphorylates various effector proteins and TF (therefore causes rapid and slow responses) - Termination
- protein tyrosoine phsphatases terminates signal
- strips phosphate residue from tyrosine (which means that proteins cannot bind to the RTK)
- a lot of tyrosine phosphatases means short signal time
