CSF chapter 15

GAP

ENHANCES GTP HYDROLYSIS rate of gtpases

Responses to signal occur in seconds

Protein phsophorylation

Paracrine

extracellular signal in the vincinity of the cell that secretes it and activates signaling in the surrrounding cell

Kinase

enzyme phosphorylate protein by transferring the terminal phosphate from ATP onto serine, threonine, or tyrosine

Endocrine

Releases hormones that are distributed to the rest of the body

Receptor desensitization

endocytosis of receptor followed by degradation of lysosome in response to a signal is

SH3

Bind to proline rich sequences

Receptors

Ion channel, GPCR, enzyme coupled

(NOT monomeric g proteins)

Phosphatases

Remove phosphate group in PROTEINS not GTP

Positive feedback

signaling molecule generate strong response that persists even after signaling molecule is REMOVED

Second messengers

amplification of signal generated when receptor whatever signaling molecules

GEF

activation of proteins lead to activation of monomeric gtpase by RELEASING GDP and bind GTP

SH2 binds to

phosphorylated tyrosines

Scaffold proteins

limit amplification and improve speed

Charged phosphoionosities bound by

Pleckstrin homology domain

Neurotransmitters

electrical to chemical

Local mediators

Secreted extracellular signaling molecules that work in the neighborhood they are released in

Paracrine

farthest away as well

a subunit binds to GDP

replaced with GTP to be activated b GPCR

Inactivation of a-subunit of G protein

GAP activity of RGS

cAMP synthesized from ATP by

adenylyl cyclase

PKA activated by binding cAMP onto

REGULATORY subunits

Negative feedback long delay

oscillatory response

NO diffuse to stimulate cGMP by binding to

Guanylyl cyclase

Increase in cAMP levels by extracellular signals balanced by breakdown of cAMP enzyme

cAMP phosphodiesterase

Activation of PLC by g protein leads to

cleavage of inositol phospholipids

IP3 leads to

release of calcium from ER to cytosol

NOS deaminized from

arginine

Chlora toxin activates alpha subunit of GS which

inhibits GTP hydrolysis of a-subunit

Exposure… desensitization of GPCR by

binding arrestin to phosphorylated GPCR

Which mutation of regulatory subunit of PKA would lead to permanent inactive state

mutation in regulatory subunit that prevent release of catalytic subunit

Nuclear receptors

active or repress transcription based on the type of receptor

PI3-kinase

counteracted by PTEN phosphatase

Notch is NOT

released by its tail to activate transcription (NO IT IS TRANSLATION)

(it is a cell surface receptor and activated by proteolytic processing cleavage)

Notch

Proteolytic cleavage y secretase

Tail released to activate TRANSLATION

Irreversible

Cell surface receptor

Mutations that disrupt the protease activity of gamma secretase will

inhibit transcription of notch target genes

Mutations of SH2 domain of Grb adaptor that inhibit recognition of RTK will lead to

inhibition of GTP binding to Ras

ATK-dependent regulation of BAD

Absence survival, BAD inhibits Bcl2

Presence survival, AKT phosphorylated

Presence survival, Bcl2 active

RTK-A activated by binding to GF. Which mutation inhibit dimerization of RTK?

mutation prevent RTK-A from binding to GF

Activation EGF includes

conformational change in receiver

AKT and ERK activate mTORC1 by phosphorylating and inhibiting which GAP

TSC

Final kinase in MAP kinase

Erk

mTORC1 is sensitive to

rapamycin

GEF activates Rag-GTPase is

Ragulator

GAP inactivates Rag GTPase is

Gator 1

Mutations inhibit TSC activity leads to tuberous scelorsis due to

high mTORC1 activity

Enhance Gator1 GAP activity leads to

inhibit mTORC1 activity

Absence Wnt

b-catenin degraded

With wnt

b-catenin accumulates

Degrade of b-catenin by proteasome stimulated by

phosphorylation of b-catenin by GSK3 and CK1

Which occurs of B-Catenun unable to bind to LEF1/TCF in presence of WNT signal

Groucho remain bound to LEF1/TCF

Which Sos recruits it to plasma membrane so it is close proximity to Grb2

PH

Mutations altering GPCR binding interface in arrestin to

prevent desensitization of GPCR

Notch to be recognized by delta it has to be

transported to plasma membrane

PI3 kinase phosphorylates

Phospholipids

Which enzyme bound to cytosolic plasma membrane converts PI(4,5)P2 to IP3 and DAG

Phospholipase C-Beta

Why doesnt beta of trimeric g protein need a lipid anchor?

uses gamma anchor OHHH

Activation of AKT by PI3k

phosphorylates lipids that create docking site for AKT

G proteins bound to GPCR

at intracellular side of plasma membrane

Mutations in Ras, which permanent activation of Ras signaling?

inhibiting Ras-GTPase activity

Kinases activated by binding DAG (whatever)

Protein Kinase C

Local mediators for Drosopilia

Wnt

Sharpen cellular response

Positive feedback

more than 1 phosphate

more than one signal molecule

(not forward and back)

Nuclear Receptors

Activate and repress transcription

SH2 and PTB bind

phosphorylated tyrosine

PH bind

phosphoionositde

Coincidence detector

requires BOTH signal A and signal B

Quickest

Phosphorylation

Short delay negative feedback

rapid shut off and produces ADAPTATION

G proteins

Alpha binds to BY complex

B can bind to plasma membrane because it is bound to Y complex

RGS

GAP protein in GPCR that hydrolyze a-GTP to a-GDP

PKA

cAMP binds regulatory subunits and RELEASES catalytic subunits

GPCR activates Gq that activated PLC-B

Cleaves PI(4,5)P2 that cleaves

• IP3: open Ca2+ ER channels

• DAG: activate PKC

Transautophoshorylation

Receptors RTK dimers phosphorylate each other

EGFR

Conformational chance in RECIEVER only

If Ras-GAP

GTP hydrolysis happens

Without signal

BAD inhibits Bcl2

WITH signal

AKT phosphorylated

Bcl2 active

mTORC1

sensitive to rapamycin

Activate by Rag-GTP and Rheb-GTP

RAG system

Ragulator: GEF (activate mTORC1)

Gator1: GAP (inhibit mTORC1)