BI203 Lecture 21: Cell Signaling - Slides 85-97 (MAP Kinase Pathway and Signaling Networks) Flashcards
___ ___ pathway - A cascade of protein kinases that is highly conserved in evolution, found in all eukaryotic cells.
MAP Kinase pathway
___ ___ are serine/threonine kinases.
MAP kinases
MAP kinases were initially found in mammalian cells belonging to the ___ family.
ERK (extracellular signal-regulated kinase) family
___ ___ ___ pathway - Key pathway regulating animal cell proliferation.
ERK MAP Kinase Pathway
The role of ERK signaling emerged from studies of ___ proteins, first identified as the oncogenic proteins of viruses that cause sarcomas in rats.
Ras
Ras is activated by ___ ___ ___ ___ (GEFs) that stimulate exchange of GDP for GTP.
Guanine nucleotide exchange factors (GEFs)
Ras-GTP activity is terminated by GTP hydrolysis, stimulated by interaction of Ras-GTP with ___ ___ (GAPs).
GTPase-activating proteins (GAPs)
Mutations in many human cancers keep Ras in an active ___ state
GTP-bound
Autophosphorylation of ___ leads to binding of Ras GEFs (Activation of Ras).
RTKs
Activation of Ras leads to activation of the ___ ___.
Raf kinase
Raf kinase then phosphorylates and activates a second protein kinase ___.
MAP
MAP then phosphorylates and activates the MAP kinase ___.
ERK (extracellular signal-regulated kinase)
ERK phosphorylates a variety of proteins involved in cell ___.
proliferation
Some activated ERK proteins go to the nucleus, where they regulate transcription factors by phosphorylation.
A primary response to growth factor stimulation is rapid transcription of ___ genes.
immediate-early genes
Rapid transcription of immediate-early genes is mediated by a regulatory sequence called the ___ ___ ___ (SRE).
serum response element (SRE)
The serum response element (SRE) is recognized by transcription factors including the ___ ___ ___ (SRF) and ___.
serum response factor (SRF), Elk-1
Many immediate-early genes encode transcription factors.
Their induction leads to altered expression of a battery of other downstream genes called ___ ___ genes.
secondary response genes
Specificity of MAP kinase signaling is maintained partly by physical association on ___ proteins.
scaffold proteins
The four main pathways which can regulate cell proliferation and survival:
cAMP pathway, PI 3-kinase/Akt & mTOR pathways, MAP kinase pathways
Activity of signaling pathways is controlled by ___ ___.
feedback loops
___ is the interaction between signaling pathways.
crosstalk
G protein-coupled receptors can be linked to MAP kinase signaling pathways by ___, which are scaffold proteins.
β-arrestins
β-arrestin serves as a ___ protein for Raf-MEK-ERK signaling, linking this MAP kinase pathway to G protein-coupled receptors.
scaffold protein
Multiple signaling pathways interact with one another to form ___ ___ within the cell.
signaling networks
