Cell Signaling Flashcards
What is the general structure of RTK’s?
Single pass transmembrane proteins with extracellular ligand binding domain and intracellular protein kinase domain
What common critical functions do RTK’s perform?
Signal pathways important for cell proliferation and tissue repair
Name four signaling protein domains that recognize P-RTK and what they recognize
SH2 and PTB: p-Tyr
SH3: proline-rich
PH: lipids (PIP2, PIP3)
Why is it important that each RTK contains several p-tyr residues?
It can interact with several different SH2 proteins at the same time, simultaneously activating different pathways
Name the major players in the MAPK pathway in order. Which one is the GTP/GDP exchange factor? Which one requires the GEF activity?
GRB2 SOS (GEF) Ras (requires GEF activity of SOS to attach to cell membrane and activate) Raf MEK (phosphorylated by RAF) MAPK/ERK (phosphorylated by MEK)
40% of solid tumors contain a mutation in ____
Ras
What are four ways to terminate the MAPK pathway?
Spontaneous hydrolysis of GTP by Ras
Ras-GAP hydrolyzes Ras bound GTP
Protein phosphatases that deactivate every component of the pathway
Internalization of the receptor
Name the sequence of events in the PI3K pathway
PI3K phosphorylates PI PI3K binds RTK (PIP2) and produces PIP3 Cytoplasmic AKT is recruited and activated by PIP3 AKT is phosphorylated by PDPK1 AKT phosphorylates its targets
What does TSC1/TSC2 complex do? What happens when AKT acts on it?
TSC1/2 is a GTPase activating protein (GAP) for Rheb. When it is phosphorylated by AKT it is inhibited, causing an increase in GTP bound Rheb
What activates mTORC1?
Rheb/GTP
Activated mTORC1 results in ____
upregulated protein translation and increased cell growth
Name an mTORC1 inhibitor
rapamycin
How is the PI3K signal terminated?
PTEN phosphates dephorsphorylate PI3K
Briefly describe the PLCg pathway
PLCg hydrolyzes PIP2 and produces IP3 and DAG
IP3 binds the ER and releases calcium into the cytoplasm
DAG activates PKC
Describe the general structure of G protein coupled receptors
They are 7-pass transmembrane proteins with an extracellular N terminus and cytosolic C terminus
Describe the general structure of G proteins
They consist of three subunits, alpha, beta, gamma subunits. The alpha subunit has RAS-like GTPase activity. Beta and gamma form a complex
Describe the action of the G protein alpha subunit
GPCR facilitates exchange of GDP for GTP on the alpha subunit. This causes alpha to dissociate and bind its downstream targets
How is the GPCR pathway signal terminated?
Alpha hydrolyzes its bound GTP with the help of RGS and reunites with beta-gamma
How is cAMP concentration regulated?
Changing the concentration of adenylyl cyclase or phosphodiesterase
cAMP binds to and activates ___
cAMP-dependent protein kinase or protein kinase A (PKA)
Name some PKA substrates
phosphorylase kinase glycogen synthase hormone sensitive lipase perilipin CREB
IP3 is important for control of what intracellular ion via what messenger protein?
Calcium via calmodulin
Name two ways GPCRs can be regulated
Phosphorylation by PKA and PKC
Phosphorylation by GRKs
What type of signaling pathway do vision, smell, and taste use?
GPCR’s
Describe the sequence of events of rod cell signaling
Receptor rhodopsin activated by light
Rhodopsin activates G protein transducin alpha subunit
GTP-alpha subunit of transducin activates cGMP PDE, decreasing concentration of cGMP
cGMP gated channels close, causing hyperpolarization
What is the G protein specific to the smell pathway?
Golf
What are the GPCR’s responsible for umami, sweet, and bitter taste?
T1R1/T1R3
T1R2/T1R3
T2R
What G protein is specific to the taste pathway?
Gustducin
