Lecture 3 & 4 - Cell Signaling

hormonal signaling

extracellular signal secreted into bloodstream and broadcast to whole organism

paracrine signaling

extracellular signal diffused locally through extracellular fluid

autocrine signaling

type of paracrine signaling where a cell responds to itself

neuronal signaling

signals over long distances but to specific targets rather than the whole body

contact dependent signaling

cells must make direct physical contact through membrane bound signal molecules

kinase

activates a protein via phosphorylation

phosphatase

inactivates a protein via dephosphorylation

G protein

large GTP binding protein that relays messages from GPCR; has intrinsic GTPase activity, meaning it will eventually hydrolyze its own GTP to GDP and inactivate itself; can activate the enzymes AC or PLC

monomeric GTPase

small GTP binding protein; activates using GEFs (guanine nucleotide exchange factors) to add GTP, and inactivates using GAPs (GTPase activating proteins) to hydrolyze it into GDP

3 types of cell surface receptors

ion channel coupled receptors, GPCRs, enzyme coupled receptors

Gs

G protein that stimulates AC

Gi

G protein that inhibits AC

Gq

enzyme that stimulates PLC

adenylyl cyclase AC

makes second messenger cAMP (from ATP), which then binds to PKA to catalyze a phosphorylation cascade; activated by Gs and inhibited by Gi

phospholipase C PLC

makes second messengers IP3 and DAG (from PIP3); IP3 promotes Ca2+ influx, which along with DAG binds to PKC to catalyze a phosphorylation cascade; activated by Gq

nitric oxide NO

second messenger signaling molecule that diffuses into neighboring cells to activate guanylyl cyclase GC, which makes cGMP from GTP and causes a cascade that relaxes target muscle

RTK signaling pathway mechanism

ligand binds to extracellular domain, causing dimerization of two RTKs and the phosphorylation and activation of their intracellular tyrosine tails, which serve as docking sites for other proteins; this triggers a signaling cascade; eventually inactivated/dephosphorylated by tyrosine phosphatases (unlike GPCRs who could terminate themselves by hydrolyzing their own GTP to GDP)

tyrosine phosphatase

dephsophorylates and inactivates RTKs

receptor tyrosine kinases (RTKs)

largest class of enzyme coupled receptors, usually causes slow responses and changes in gene expression; involve PLC as well as the signaling protein Ras

Ras

type of monomeric GTPase signaling protein involved in most RTKs; triggers phosphorylation cascade, specifically mitogen activated protein (MAP)-kinase signaling, to lead to changes in gene expression

MAP kinase signaling module

signaling pathway initiated by Ras signal protein in RTK cascade; leads to change in gene expression

Akt / Protein kinase B (PKB)

proteins promoting cell growth by activating Tor, which enhances protein synthesis and inhibits protein degradation

nuclear receptors

steroid hormones small and hydrophobic enough to pass through target cell membrane and bind to receptors in the cytosol or nucleus