Cell Signaling Flashcards
Describe the role of adenylyl cyclase in second messenger activation.
Adenylyl cyclase is activated by binding of a ligand to a stimulatory G protein. AC cyclizes ATP to cAMP, which then goes on to activate PKA or control ion channels. AC is deactivated by ligand binding to an inhibitory G protein.
What mechanisms are used to terminate signals?
- Terminators
- Degradation
- Desensitization
- Protein phosphatases
- GTPases (GTP → GDP)
- Phosphodiesterases
cAMP is released upon binding of a ligand to the receptor on the cell surface. The release of cAMP activates pathways within the cell. cAMP is an example of what type of messenger?
Secondary messenger - cAMP is an intracellular messenger amplifying the signal from the primary messenger that binds to the cell surface
What molecule regulates activity of G proteins and to which subunit does it bind?
GTP - Activates G protein
GDP - Inactivated G protein
Both bind to the alpha subunit
Describe the structure and function of heterotrimeric and monomeric G proteins.
Heterotrimeric - three subunits (alpha, beta, gamma), regulates second messengers
Monomeric - single subunit that resembles the alpha subunit of the heterotrimeric protein, relays signals to intracellular kinases
What is the signaling molecule for the Wnt/beta-catenin pathway and what are the functions of the pathway?
Beta-catenin
The pathway regulates embryo development and tissue homeostasis. Irregular activation of the pathway contributes to tumor growth.
These types of receptors have three domains in a single protein chain - ligand-binding portion, alpha-helical transmembrane domain, and catalytic domain.
Single transmembrane receptors
What amino acid residues are often phosphorylated by PKAs?
Serine, threonine, tyrosine
Describe the mechanism and result of cGMP hydrolysis.
G(t) proteins are activated by light binding to Rhodopsin (GPCR). The alpha subunit activated cGMP phosphodiesterase to hydrolyze cGMP to GMP. Na+ channels close and hyperpolarize the cell, sending an excitatory signal down the neural pathway.
Describe the PI3-Kinase signal transduction pathway. Be sure to include the pathway function, transduction steps, and signal termination.
PI3-Kinase binds phosphorylated tyrosine on the catalytic receptor. The activate PI3 kinase phosphorylates membrane phospholipids to generate PIP3. PIP3 recruits Akt (PKB) to phosphorylate Bad. This process promotes cell survival. The signal is terminated by dephosphorylation of PIP3 by PTEN.
What are the functions of JAK/STAT proteins?
JAK/STAT proteins are activated by cytokine binding and regulate immune cell proliferation.
What is the function of steroid hormone receptors
Increase gene transcription
Describe the signaling mechanism of single transmembrane receptors, such as Tyrosine kinase and JAK-STAT receptors.
Upon ligand binding, the protein dimerizes. The kinase domain becomes activated and phosphorylated an amino acid on the receptor. The signal is then relayed through signal-transducing proteins.
What are the main types of cell signaling?
Autocrine - individual cell
Paracrine - nearby cell
Endocrine - distant cell
What is the structure of G protein-coupled receptors (GPCR)?
Heptahelical - seven transmembrane alpha helices
What is the result of activation of Phospholipase C by a G protein?
Binding of a ligand to G(q) protein receptor activates PLC. PLC cleaves PIP2 to form IP3 and DAG (diacylglycerol). IP3 acts as a second messenger to release sequestered Ca2+. DAG activates PKC to phosphorylate other proteins.
Describe the signaling method of the Tyrosine Kinase receptor.
The TK becomes activated by binding of growth factors and insulin to the receptor. The tyrosine kinase domains activate one another through trans auto-phosphorylation. SH2 adopter proteins bind with phosphorylated tyrosine to relay the signal intracellularly.
What are the major function domains of intracellular hormone receptors?
Hormone/ligand-binding domain - COOH terminal
Gene regulatory domain/transcription activation domain - NH2 terminal
DNA-binding domain - highly conserved, zinc finger motifs for DNA binding
What are the general steps of cell signaling?
- Release of 1st messengers
- Reception of messengers by the target cell
- Signal transduction
- Generation of cellular response
Describe the activation mechanism of a GCPR.
A ligand binds the extracellular portion of the GCPR. The GCPR undergoes a conformational change and the alpha subunit of the G protein hydrolyzes GDP to GTP. Activation of the protein by GTP causes the alpha subunit to dissociate from the beta-gamma subunits. The activated alpha subunit targets enzymes or ion channels to activate second messengers
True/False. JAK/STAT proteins have intrinsic protein kinase activity activated by cytokine binding.
False. JAK/STAT proteins have NO intrinsic protein kinase activity but are associated with tyrosine kinases (JAK). When a cytokine binds, JAK phosphorylates one another and the protein. STATS bind and are also phosphorylated before being released and translocated to the nucleus for gene transcription.
What results from the cleavage of PIP2?
Cleavage produces IP3 and DAG. IP3 targets CA2+ channels to release Ca2+. DAG activates PKC.
