Lecture 21: Signal Transduction

signal transduction

extracellular signal is amplified and converted to a cellular response

reception

transduction: signal recoded amplified, and transmitted

response

signal transduction process (steps)

signaling enzymes

binding interactions

protein conformation

post-translational modification

subcellular localization

what are some ways that allow the system to go from an on state to off state?

catalyze the rxn

write/erase signals in a controlled fashion

provide simple mechanisms for signal amplification

what is the role of enzymes in signal transduction?

protein kinase

catalyze protein phosphorylation by transferring γ-phosphate of ATP to side chain of selected amino acid

hydroxyl of serine (Ser), threonine (Thr), and tyrosine (Tyr)

where does protein phosphorylation occur on eukaryotes?

two lobed structure

active site (catalytic)

activation loop (regulatory)

structure of eukaryotic protein kinase

• binding activator protein/releasing inhibitor protein

• producing small allosteric regulators

• phosphorylation of activation loop

what are ways that upstream input signal can control the activity of protein kinase?

kinase cascade

activation of upstream protein kinase leads to phosphorylation and activation of downstream protein kinase

changes the chemical property

• polar uncharged to negative charge

• isoelectric point

how does protein phosphorylation change amino acid chemically?

protein phosphatase

eraser of protein kinase (phosphorylation)

serine/threonine phosphatase

tyrosine phosphatase

dual specificity phosphatase

3 phosphate subfamilies

both can be controlled and regulated based on upstream input signal

what is the benefit of the unidirectional cycle between protein phosphatase and protein kinase?

G proteins

bind and hydrolyze GTP

they can change their shape based on if a nucleotide is bound or not

• GTP bound: on

• GDP bound: off

how do G proteins serve as molecular switches?

conformation change of the G protein which decides if the effector will bind to it or now

what happens when the γ-phosphate binds and interacts with switch 1 and 2?

GEFs (guanine nucleotide exchange factors)

accelerate GDP/GTP exchange thus activating G proteins

GAPs (GTPase-activator proteins)

accelerates GTP hydrolysis thus inactivating G proteins