HRR: cell signaling Flashcards
Name the main types of cell signaling and briefly describe them
- Autocrine: cell signaling to itself
- Paracrine: cell signaling to a nearby cell
- Endocrine: cell signaling to a far away cell
- Cell to cell: cells signaling to a cell right next to them
Specify the main classes of plasma membrane receptors
- Transmembrane: integral membrane proteins
- Intracellular receptors: receptors are found within the cytoplasm. They bind to ligands that either diffuse or are transported into the cytoplasm and move to the nucleus to promote transcription. They function as transcription factors that directly regulate transcription of target genes.
G- receptors: structure and example
they have 7 transmembrane receptors and an N terminus containing the ligand binding domain. They’re heterotrimeric (alpha, gamma, beta); cAMP and IP3/DAG
receptor tyrosine kinases: structure and example
single-pass transmembrane proteins; intrinsic kinases that phosphorylate on tyrosine. EGF and IR pathway!
JAKSTAT receptors: structure and example
do not have an intrinsic kinase and use JAKS instead; utilize tyrosine! STAT
receptor serine-threonine kinases: structure and example
use intrinsic kinase and serine/threonine; TGF beta
Specify 4 types of Gα subunits, their molecular targets, and the 2nd messengers that
are generated following ligand binding to a GPCR
Gas: stimulates adenylyl cyclase, cAMP
Gai: inhibits adenylyl cyclase, cAMP
Gaq: stimulates phospholipase Cb, IP3 and DAG
Ga(12/13): stimulates cytoskeletal proteins, GDP-GTP exchange
describe the activation of PKA
adenylyl cyclase converts ATP to cAMP. 4 cAMP molecules bind to the regulatory subunits of PKA, which then dissociate from the catalytic units. Those units are then active and can go on to phosphorylate and regulate target proteins. subunits of and activates protein kinase.
describe the activation of PKC
phospholipase C cleaves a lipid in the membrane called IP2 into IP3 and DAG. DAG stays in the membrane and IP3 migrates to an IP3 sensitive calcium channel, causing calcium to be released into the cell. Calcium will bind to PKC, then PKC travels to the membrane and binds to the DAG in the membrane; it is then activated.
give the starting ligand and ending signal product for classic receptor tyrosine kinases
EGF, map kinase
give the starting ligand and end signaling product for receptor tyrosine kinases using alpha/beta subunits
insulin, PKB
give the starting ligand and ending signaling product for serine-threonine receptors
TGF beta, SMADS
- Describe the EGF pathway
uses a tyrosine kinase receptor; A ligand binds to a domain on the extracellular surface and promotes dimerization. This dimerization and activation of intrinsic or associated kinase. Autophosphorylation then occurs. Adaptor proteins then bind to the dimer and a complex consisting of SH2 protein, grb/GEF, and commonly RAS-GDP assembles. GDP becomes GTP, allowing RAS to bind to RAF. This initiates MAP kinase pathway
What are some functions of PKB
Preventing apoptosis and increasing protein synthesis
- Describe the IR pathway
uses a tyrosine kinase receptor;
1. Insulin binds to the alpha subunit, causing a conformational change and cross phosphorylation on the beta subunit.
2. IRS1 binds to activated IR and becomes phosphorylated on tyrosine. This provides SH2 domains for other docking proteins and an activated PI3 kinase.
3. PI3 clips PIP2 to PIP3, which then recruits PKB.
4. PKB is then phosphorylated and activated by PDK1.
5. PKB then dissociates from the membrane and is activated
Describe JAK-STAT receptors and their signaling
A ligand binds to a domain on the extracellular surface and promotes dimerization. This dimerization and activation of JAKs. JAKs then phosphorylate each other and the receptor. These phosphorylated sites serve as SH2 domain binding sites. STATs then bind and become phosphorylated by the receptor. The STATs dissociate, dimerize, and translocate to the nucleus.
Describe the TGF-β pathway
Ligand binds to a type II receptor, which then recruits a type I receptor. The type I is phosphorylated on serine by the type II, which activates the intrinsic kinase of type I. SMADs then bind and become phosphorylated. Upon phosphorylation, SMADs dissociate and translocate to the nucleus.
Describe some regulations associated with TGF signaling
Stimulation of extracellular matrix synthesis, anti-proliferation, metastatic cancer
What is the negative regulator of cAMP?
cAMP phosphodiesterase
Describe how G protein receptors work
-In the resting state G alpha subunit is bound to GDP.
-Upon ligand binding the G-protein undergoes a conformational change that results in the release of GDP and the binding of GTP. GDP to GTP exchange causes the α subunit to dissociate from the β and γ subunits
-GTP bound Gα can then bind to target enzymes such as adenylyl cyclase which is then activated to catalyze the reaction of ATP→cAMP.
-When GTP is hydrolyzed to GDP, Gα dissociates from the target protein and is available
to re-associate with the G proteins to reform the resting G-protein coupled receptor
What receptor type is targeted by drug companies?
G protein
What proteins are calcium regulated?
Cl channels, K channels, PKC, adenylyl cyclase, nitric oxide synthetase
Describe the regulator of free calcium
Calmodulin; each calmodulin can bind 4 calcium molecules
Describe calmodulin in relation to muscle contraction
Calmodulin binds to calcium and brings it to MLCK. This allows for a conformational change that activates the kinase. The kinase can then activate myosin light kinase and produce contraction
Describe a large signaling impact of nitric oxide
activate guanylate cyclase to making cGMP and activate PKG
What are the major ways of regulating ion channels? What are their usual organizations?
Ligand gating and volage gating; pentamer, tetramer, or trimer
What pathways are commonly associated with cancer?
RAS and IP3
what can MAP kinase stimulate?
transcription
