CELL SIGNALING - 2 Flashcards
intrinsic enzyme activity or associates directly with an enzyme
cytosolic domain
transmembrane proteins with their ligand-binding
domain on the outer surface
enzyme coupled receptors
example of enzyme coupled receptor that are important in cell functions (eg. cell to cell communication, movement, cell division, etc.)
receptor tyrosine kinase
classified number of RTK’s and subclasses
60 human RTK, 20 subfamilies
how is RTK activated in the cytosolic side
binding of signal protein to the ligand binding domain
the binding of the ligand-binding domain causes _______ bringing two cytoplasmic domains together
dimerize
example of two cytoplasmic domains coming together due to the activation cause by the ligand-binding domain in the RTK
insulin receptors
signal molecule that changes the conformation of protein receptors, activating the kinase domains
epidermal growth factor
serve as a switch to trigger the assembly of an intracellular signaling complex
receptor phosphorylation
families of monomeric GTPases; relays the signals from cell-surface receptors
Ras superfamily
coordinately spreads the signal along several distinct downstream signaling pathways
signaling hub
types of Ras proteins on humans
H-Ras, K-Ras, and N-Ras
required when RTK signals the nucleus to stimulate cell proliferation or differentiation
Ras proteins in humans
two classes of signaling protein that are regulated by Ras proteins
Ras guanine nucleotide exchange factors(Ras-GEF)
Ras GTPase-activating proteins (Ras-GAP)
dissociation of GTP and the uptake of GDP activates the Ras
Ras guanine nucleotide exchange factors(Ras-GEF)
the hydrolysis of GTP inactivates the Ras
Ras GTPase-activating proteins (Ras-GAP)
type of Ras-GEF that mediates the activation of Ras protein through RTK
sons-of-sevenless
signaling molecule that promotes Ras activation; required for the formation of photoreceptor cell 7
sevenless
relays the signal sent by the activated Ras protein downstream by phosphorylation; mediates different responses inside the same cell
mitogen activated protein kinase module(MAP kinase module)
three components of MAP kinase module
MAPK (Erk), MAPKK (Mek), MAPKKK (Raf)
MAP kinase module that enters the nucleus; phosphorylates transcription regulatory complexes
MAPK (Erk)
conveys the signal from the cell surface towards the nucleus and alters the pattern of gene expression
Ras-MAP kinase-signaling pathway
prevents cross talks in between parallel MAP kinase modules
scaffold proteins
proteins that responds to different kinds of cell stresses (UV, heat shock, osmotic stress)
JNK and p38 protein
regulates both the actin and microtubules that control the cell shape, polarity, motility, and adhesion; activated by GEF’s and disabled by GAP’s
Rho family monomeric GTPases
surface of motor neuron that guides the migrating tip of the axon (growth cone) to its muscle target; Eph family of RTK’s
ephrin family
activates RhoA (RhoA-GTP); activated by phosphorylation from RTK
ephexin
controls gene expression of Tim and Per gene
circadian rhythm
controls cell face choices and regulates the pattern formation and continued renewal of the tissues; uses wildly in animal development
Notch receptor protein
lateral inhibition or contact dependent cell action; binds to notch receptor proteins
delta
single pass transmembrane proteins that requires proteolytic processing to funciton
notch proteins
ACTIVATION OF NOTCH PROTEIN: Overview
- delta binds to the notch receptor proteins
- the plasma membrane bound proteases cleaves of the cytoplasmic tail of notch
- the cleaved off tail translocate to the nucleus to activate the transcription of notch response genes
[the cleaving of the tail converts it from being a transcriptional receptor to a transcriptional activator]
three steps of notch receptor proteolytic cleavage
1st - biosynthesis
2nd - binding of delta
3rd - cutting of the cytoplasmic tail
the cleaved tail of the notch genes
y-secretase
signal molecules that act as local mediator and morphogens
Wnt proteins
coordinates the polarization of cells in the plane of a developing epithelium
planar polarity pathway
regulates the proteolysis of the malfunctional protein β-catenin
Wnt-β-catenin pathway
phosphorylates the β-catenin
casein kinase 1 (CK1) and glycogen synthase kinase 3 (GSK3)
holds the casein β-catenin protein complex altogether
axin and Adenomatous polyposis coli (APC)
Wnt/β-catenin pathway: OVERVIEW
- wnt binds to the frizzled protein and its co-receptor, LDL receptor
- the activated receptor complex of frizzled and LDL recruits dishevelled scaffold proteins
- the dishevelled scaffold proteins promotes the phosphorylation of LDL receptor using CK1 and GSK3
- axin is brought to the receptor complex, and is inactivated
- this disrupts the degradation complex of β-catenin
- the pattern of gene transcription is altered
[from signal repression to transcriptional activation]
an important regulator of cell growth and proliferation
Myc
inhibits the proteins ability to bind β-catenin, causing β-catenin to accumulate in the nucleus causing the transcription of c-Myc and other Wnt target genes
Wnc/β-catenin pathway
secreted signal molecules and acts as local mediators and morphogens (e.g. Wnt proteins)
hedgehog proteins
genes that encode hedgehog proteins
sonic, desert, and indian hedgehog
hedgehog proteins are mediated by a latent transcription regulator called; absence of hedgehog proteins causes this regulator to be broken down to fragments, silencing hedgehog proteins
Cubitus interruptus (Ci)
keeps the unprocessed Ci out of the nucleus
fused and costal 2 scaffold protein
three transmembrane proteins that bind the hedgehog protein
patched, iHog, smoothened
recruits the protein complex Ci, fused and, costal 2
smoothened
induces endocytosis and degradation; inhibits the activity of patched
binding of hedghog to iHog and patched
inhibits hedgehog signaling; negative feedback
genes for patched
recognize pathogens and activate this pathway in triggering innate immune responses
Toll receptors in Drosophila; Toll-like receptors invertebrates
they trigger multiprotein ubiquitylation and phosphorylation cascade that releases NFKB from an inhibitory protein complex when activated
tumor necrosis factor (TNF ) and interleukin-1 (IL1)
inhibitory protein; bind tightly to the dimers and hold them in an inactive state within the cytoplasm of unstimulated cells
IκB
translocate to the nucleus and turn on the transcription of genes that participate in inflammatory and innate immune responses
RelA, RelB, c-Rel, NFKB1, and NFKB2
types of IκB
IκB α, β, and ε
activates the gene that encodes IκBα
NFKB
inactivates NFKB proteins; negative feedback inhibition
IκBα
negative feedback produces two types of NFκB responses; induce different patterns of gene expression
TNFα-induced responses
hydrophobic signal molecules that diffuse directly across the plasma membrane and bind to intracellular receptors (transcription regulators); serves both as intracellular receptors and as intracellular effectors
nuclear receptor superfamily
nuclear receptor superfamily with no known ligand
orphan nuclear receptors
bind to specific DNA sequences adjacent to the genes that the ligand regulates
nuclear receptors
alters the conformation of the receptor protein; causing the inhibitory complex to dissociate; bind coactivator proteins that stimulate gene transcription
ligand binding
internal oscillators that control diurnal rhythms; enables an organism to anticipate the regular daily changes in its environment and take appropriate action in advance
circadian clocks
controls our diurnal cycles of sleeping and waking, body temperature, and hormone release; found in the suprachiasmatic nucleus of the hypothalamus
SCN cells
forms a heterodimer → dissociates and transported into the nucleus; gene products switches off the transcription of their own genes
Tim (timeless) and Per (period) genes
cell-surface receptors in plants:
receptor serine/threonine kinases and leucine-rich repeat (LRR) receptor kinases
regulate growth and differentiation of plants
brassinosteroids
small gas molecule that promote fruit ripening, leaf abscission, and plant
senescence; stress signal in response to wounding, infection, flooding, so on.
ethylene
located in the endoplasmic reticulum; dimeric, multipass transmembrane proteins
ethylene receptors
stimulates the ubiquitylation and degradation in proteasomes of nuclear transcription regulator EIN3; copper-containing ethylene binding domain
CTR1
initiation and positioning and helps plants flower and bear fruit; signals the plant to grow toward light, grow upward rather than branch out, and grow roots downward
auxin (indole-3-acetic acid)
transport systems of auxin
influx transporter proteins and efflux transporter proteins
light sensitive proteins; covalently attached light absorbing chromophore, which changes its shape in response to light and then induces change in the protein’s conformation
photoproteins
activated by red light and inactivates in far-red light; translocate into the nucleus and activates transcription regulator
phytochromes
tendency of plants to grow toward light (phototrophism) are caused by
phototropin
flavoproteins; sensitive to blue light; involved in the repair of ultraviolet induced DNA damage
cryptochromes
