15 C - Cell Signaling (Enzyme coupled receptors)

RTKs, Ser/thr

Enzyme coupled receptors can be _______ or Receptor ______/______kinases

dimers, phosphorylate

Upon binding to ligand RTKs (Receptor Tyrosine Kinases) monomers come together to form ______, and these (previous answer) _______ each other and this stimulates assembly of an intracellular signaling complex that interact with receptor via interaction domains.

EGF, conformational

Special case:

Upon binding _____ , the receptor dimerizes.

• The tyrosine kinase domain unlike other RTKs is activated by _____ changes in the activator domain
  that pushes against the receiver kinase domain and activates the kinase activity of only the receiver domain, which then phosphorylates itself and phosphorylates
  the activator.

EGF

Epidermal Growth Factor means

SH2

Intracellular signaling proteins with ____ domains can bind to activated receptor kinases (RTKs)

PTB

phosphotyrosine binding domains

SH2

Src homology 2

D

The two monomers in a receptor tyrosine kinase (RTK) dimer phosphorylate each other and the process is called..................
A- Nucelotide exchange
B- Ubiquitination
C- Serine Phosphorylation
D- Trans-autophosphorylation

Ras

The monomeric GTPase _____ superfamily mediates signaling by most RTKs

Ras

a monomeric GTPase that binds GTP

GEF

Ras ___ turns Ras ON

GAP

Ras ___ turns Ras Off

GAP

GTPase Activating Factor

GEF

Guanine Nucleotide Exchange FactoR

RTK, Ras-GEF (Sos)

SH2 domain of Grb2 adaptor binds to activated _____ and TWO SH3 domains bind to _____ (_____)

short

Activation of Ras is _______-lived

• tyrosine phosphatases quickly reverse RTKs

• Ras-GAPs induce GTP hydrolysis

Raf

MAPKKK = ____

Mek

MAPKK = ____

Erk

MAPK = ____

MAP

Ras Activates a _____ Kinase Signaling Module

MAPK

Mitogen Activated Protein Kinase

Scaffold proteins

_______ _______ help prevent cross-talk between parallel
MAP Kinase modules

inhibit, GTP, ON

Ras activating mutations _____its GTPase activity

• They keep Ras ALWAYS bound to ____and therefore it stays always in an ____ state

endocytosed

RTKs can be ______

A

Which of the following mechanisms is NOT directly involved in inactivating an activated RTK (Receptor Tyrosine Kinase)?
A- dephosphorylation by serine/threonine phosphatases
B- dephosphorylation by protein tyrosine phosphatases
C- removal of the RTK from the plasma membrane by endocytosis
D- digestion of the RTK in lysosomes

PI3K

______ generates phosphoinositide docking sites

PI(3,4,5)P3

PI3-Kinase serves as a docking site for signaling
proteins with PH domains that can bind to _______

AKT

Activated _____ promotes cell survival

phosphorylation

AKT inactivates BAD by _______.

apoptosis, Bcl2

BAD protein promotes _____ in its unphosphorylated state by inhibiting ______ (apoptosis inhibitory protein)

releases, blocks

When AKT phosphorylates BAD, BAD ______ Bcl2, which _____ apoptosis

Akt/Ekt, GTP, mTORC1

PI-3-Kinase- Akt- mTORC1 signaling pawthway

Inhibition of TSC by phosphorylation via ____ / ____ keeps Rheb in its ____ bound state, which interacts w/ ____

Gator2, GTP, mTORC1, Ragulator, lysosome

PI-3-Kinase- Akt- mTORC1 signaling pawthway

Inhibition of Gator1 by ____ keeps Rag in its ____bound state, as Rag interacts w/ ____

• Rag is also kept in this state by activation of _______ stimulated by amino acids in _______

Ragulator

Rag GEF is also called _____

cytosolic, activates, inhibits

PI-3-Kinase- Akt- mTORC1 signaling pawthway

_____ amino acids bind to receptor that _____ Gator2

• Gator2 then _____ Gator1

Gator1

Rag GAP is also called _____

PI3K, Ras, ATK, ERK, TSC

PI-3-Kinase- Akt- mTORC1 signaling pawthway

• The growth factor on activaketed RTK produces ____ and _____ which produce ______ and ______ repsectively

• These then phosphorylate (inhibit) ____

TSC

Rheb GAP is also called _____

active, GDP, inactive, no

PI-3-Kinase- Akt- mTORC1 signaling pawthway

• WITHOUT Growth Factor

  • TSC is ____ (Rheb-____)

  • mTORC1 is ____

  • cell growth?

active, active, inactive, GTP, active, yes

PI-3-Kinase- Akt- mTORC1 signaling pawthway

• W/ Growth Factor

  • _____ PI3-kinase

  • ____ Akt

  • TSC is ____ (Rheb-____)

  • mTORC1 is ____

  • cell growth?

Notch, delta

Lateral inhibition is mediated by _____ and _____ during neural cell development in Drosophila

notch

The receptor _____ is a Transcription regulatory protein

nucleus

the cleaved notch tail migrates to the _____

A

Activation of Notch is irreversible?
A) TRUE
B) FALSE

stable, transcription

WITH Wnt Signal

• B-catenin is _____

• _____ of Wnt target genes occurs

phosphorylate, unstable, off

WITHOUT Wnt Signal

• active CK1 and GKS3 _____ B-catenin, making it _____

• Wnt target genes are ____

proliferation, stem cell

B-catenin binding- promotes _____ and _____ _____ like state

cytoplasm, nucleus

Some nuclear receptors are located primarily in the ____ and then enter the ______

growth

Raptor leads to stimulation of _____ by mTOR1

Gamma secretase

In Alzheimer’s

• Mutation in _____ _____ cleaves a neuronal protein