Cell signaling part 2 Flashcards
transmembrane proteins with their ligand-binding domain on the outer surface
enzyme-coupled receptors
How is ECR different from GPCR differ in terms of cystolic domain?
Cystolic domain has intrinsic enzyme activity or associates directly with enzyme
Most common type of enzyme-coupled receptors
receptor tyrosine kinase
How many Human RTKs?
60 human RTKs
How many structural subfamilies in 60 human RTKs
20
the binding of the signal protein to the ligand -binding domain on the extracellular side of the receptor
activates the tyrosine kinase domain on the cytosolic side
Activation of cytoplasmic kinase domains of RTKs
dimerization
dimerization brings the kinase domains close to each other in an orientation that allows them to phosphorylate each other on specific tyrosines
Insulin receptor
activate kinase domains
Promoting conformational change
families of monomeric GTPases
- relay signals from cell-surface receptors
Ras superfamily
can coordinately spread the signal along several distinct downstream signaling pathways
Signaling Hub
Three major, closely related Ras proteins in humans
H-, K-, and N-ras
between two distinct conformational states
Molecular switch
How does Ras activity acts as molecular switches
GTP: on (active)
GDP: off (Inactive)
dissociation of GDP; uptake of GTP, activatingRas
Ras guanine nucleotide exchange factors (Ras-GEFs)
hydrolysis of bound GTP, inactivating Ras
Ras GTPase-activating proteins (Ras-GAPs)
Are resistant to Ras GAPs
Hyperactive mutatant forms of Ras
GEF that mediates Ras activation by RTKs
Sevenless (Sev)
Genetic screens for components of this signaling pathway led to the discovery of a Ras GEF
Son-of-sevenless (Sos)
which is an adaptor protein that links the Sev receptor to the Sos protein
Grb2
promotes the Ras activation
Sos
Short-lived signaling events that is activated by RTKs
- Tyrosine phosphorylations and Ras activation
relays the signal downstream by phosphorylation
MAP kinase
Three componens of MAP kinase module
- MAPK (Erk)
- MAPKK (Mek)
- MAPKKK (Raf)
MAP kinase module
mitogen-activated protein kinase
module
MAP Kinase module full name
mitogen-activated protein kinase module
enters the nucleus and phosphorylates transcription regulatory complex
erk
What does eark activates?
Immediate early genes (Transcription regulators)
convey signals from the cell surface to the nucleus and alters the pattern of gene expression
Ras-MAP-kinase signaling pathways
mediates different responses in the same cell
MAP kinase modules
help prevent cross-talk between parallel MAP kinase modules
Scaffold proteins
five parallel MAP kinase modules
- 12 MAP kinases
- 7 MAPKKs
- 7 MAPKKK
activated by different kinds of cell stresses (UV, heat shock, osmotic stress)
JNK and p38
reduces the opportunities for amplification and spreading of the signal to different parts of the cell
Scaffold strategy
the other class of Ras superfamily GTPases that relays signals from cell-surface receptors
Rho Family
regulate both the actin and microtubules cytoskeleton controlling cell shape, polarity, motility, and adhesion
Rho family monomeric GTPases
Family members of Rho family
Rho, Rac, and Cdc42
often bound to guanine nucleotide dissociation inhibitors (GDIs) in the cytosol
inactive Rho family GTPases
provides an example of how RTKs can activate a Rho GTPase
ephrin family
Ephrins bind and thereby activate members of the
Eph family of RTKs
migrating tip of the axon
growth cone
activates the Eph receptor
binding of ephrin pritein
repelling them from inappropriate regions and keeping them on track
growth cone collapse
activate RhoA (Rhoa-GTP)
Rho-GEF ephexin
Major changes in the behavior of a cell tend to depend on
Gene expression
carry out their effects by initiating signaling pathways that change the activities of transcription regulators
Many extracellular signaling molecules
control in gene expression
Less common
pathways that depend on ___ ___
regulated proteolysis
What does regulated proteolysis control?
control activity
What does transcription regulators control?
Location of latent
gene expression controlled by
circadian rhythm
- used widely in animal development.
- controlling cell face choices and regulating pattern formation and continual renewal of tissues
Notch protein
Notch receptor protein is known for its role in?
the production of Drosophila neural cells
contact dependent
Lateral inhibition
binds to Notch receptor protein
Delta