Cell Bio Lecture 33

Front 1

2 functions of arrestins

Back 1

physically block
adaptor for clathrin-coated pit

Front 2

binding of ligands leads to

Back 2

signaling cascade

Front 3

2 major groups of cell-surface receptors

Back 3

1)g-linked (1/3 of medical drugs target)
2)enzyme-linked--> bind small proteins (growth factors) and low concentration, act very quickly

Front 4

enzyme-linked cell-surface receptors

Back 4

-receptor tyrosine kinases
-tyrosine-kinase-associated receptors
-receptor-like tyrosine phosphatases
-receptor serine/threoine kinases
-receptor guanylyl cyclases
-histidine-kinase-associated receptors (yeast and plants only)

Front 5

receptor tyrosine kinases

Back 5

largest class
-tyr phosphorylation of small set of intracellular signalling molecules

Front 6

tyrosine-kinase-associated receptors

Back 6

receptors stably associated with tyrosine kinases

Front 7

receptor-like tyrosine phophatases

Back 7

not yet identified
remove phosphate groups from tyrosines of specific intracellular signaling proteins

Front 8

receptor serine/threonin kinases

Back 8

see handout?
phosphorylates specific serines or threonines on latent regulatory genes

Front 9

receptor guanylyl cyclases

Back 9

catalyze production of cGMP

Front 10

histidine-kinase-associated-receptors (yeast and plants only)

Back 10

activate a "2-component" signaling pathway in which the kinase phosphorylates itself on histidine and then immediately transfers the phosphate to a second intracellular signaling protein
-pivotal role in motility

Front 11

3 major characteristics of enzyme-linked cell surface receptors

Back 11

-ligand binding domain: extracellular
-one transmembrane domain
-cytosolic domain

Front 12

receptor activation generates

Back 12

"downstream" events that effect cell behavior and function

Front 13

activation of enzyme-linked receptors by

Back 13

a signaling molecule stimulates ...

Front 14

stimulates

Back 14

phosphate transfer or nucleotide exchange generating a cascade of biochemical activity that relays info to the cytosol and nucleus

Front 15

protein kinases in these pathways often act as

Back 15

molecular switches that activate a "phosphorylation cascade" during the relay of info

Front 16

what are receptor tyrosine kinases (RTKs)

Back 16

large family of single-pass transmembrane proteins which bind the following ligands:

Front 17

bind the following ligands:

Back 17

secreted: egf, insulin (igf-1), ngf, pdgf, m-csf, fgf

cell surface bound: ephrins (largest)

Front 18

intracellular signaling initiated

Back 18

-dimerization of the receptor (following the ligand binding)
-autophosphorylation (cross phosphorylation by dimerized subunits)

Front 19

7 subfamilies of receptor tyrosine kinases

Back 19

1) egf receptor
2) insulin receptor, igf-1 receptor
3) ngf receptor
4) pdgf receptor, m-csf receptor
5) fgf receptor
6) vegf receptor
7) eph receptor

Front 20

receptor dimerization

Back 20

autophosphorylation

Front 21

egf functinons as a

Back 21

monomer inducing chains to dimerize

Front 22

pdgf functions as a

Back 22

dimeric, "bifunctional" ligand that crosslinks receptors into dimers

Front 23

egfr activation of

Back 23

kinase domains

Front 24

pdgfr

Back 24

transmembrane domain
not changing
the c-terminus domain is changing

Front 25

3 ways in which signaling proteins can cross-link receptor chains

Back 25

glycosaminoglycan chain links (bound ligands)
-ephrins = largest class of ligands for receptor tyrosine kinases
-cross dimerize and auto activate

Front 26

eph receptors are the ones that

Back 26

cross dimerize and auto activate

Front 27

ephrins are in the

Back 27

extracellular space

Front 28

pdgf-receptors

Back 28

bifunctional ligand brings together

Front 29

autophosphorylated tyrosines function as

Back 29

high affinity binding sites for transient assembly of intracellular signaling complexes

Front 30

try-phosphorylationn of specific residues on the cytoplasmic tail of the receptor direct

Back 30

specific binding of important target proteins to the receptor

Front 31

try-phosphorylation of the bound target proteins then stimulates

Back 31

their activity leading to further activation and relay of "downstream" events

Front 32

try-PO4 serve as

Back 32

docking sites for proteins with sh2 domains such as tyrosine-kinase src and pi3-kinase

Front 33

activated receptor tyrosine kinase act as

Back 33

docking sites (only bind phosphorylated tyrosines) and change conformation

Front 34

src homology =

Back 34

sh2
"plug in" module allows proteins to bind to activated receptors

Front 35

pdgf receptor is a type of

Back 35

rtk

Front 36

some of docked proteins serve as adaptors to

Back 36

couple receptors to the small GTPase RAS

Front 37

SH3 =

Back 37

src homology binds proline-rich motifs

Front 38

RAS (GTPase)

Back 38

important signal mediator
-provide crucial link in intracellular signaling cascades activated by receptor tyr kinases

Front 39

large superfamily; monomeric g-proteins

Back 39

GTPases (Ras, Rab, ARF, Rho)
prenylated tail - linking to the cytoplasmic surface of the PM
-function like G alpha-subunits (trimeric G-proteins): activate when GTP bound/inactive when GDP bound

Front 40

GTPase activity is regulated by accessory proteins:

Back 40

guanine nucleotide exchange factors, GTPase-activating proteins (GAPs)

Front 41

RAS activates a

Back 41

downstream serine/threonine phosphorylation cascade that includes a MAP-kinase

Front 42

RAS provides a crucial link into

Back 42

intracellular signaling cascades activated by receptor Tyr kinases

Front 43

MAP-kinase-kinase is able to phosphorylate a

Back 43

a kinase that phosphorylates a kinase, etc.

Front 44

deregulation of the Ras signaling pathway: a route to cancer

Back 44

a variety of human tumors, show cells carry mutations of Ras genes that lead to hyperactive Ras activity

Front 45

tyrosine-kinase associated receptors

Back 45

large family of receptors that lack intrinsic tyrosine kinase activity, yet relay signals through tyrosine phosphorylation by associating with cytoplasmic tyr-kinases such as the 3 examples shown below

Front 46

cytoplasmic tyrosine kinases are stably associated and are broken into 3 kinds

Back 46

src-family
-focal adhesion
-janus

Front 47

src family kinases

Back 47

all these kinases contain sh2 and sh3 domains located on the cytoplasmic side of PM, attached via receptor and covalently attached lipid chains
-stably associated

Front 48

focal adhesion kinases

Back 48

bind to integrin receptors
at cell matrix junctions

Front 49

janus kinases

Back 49

bind to cytokine receptors
largest family of them all

Front 50

cytokine receptors

Back 50

subfamily of enzyme-linked receptors
1) largest most diverse class of receptors that rely on cytoplasmic kinases to relay signals into the cell
2) stably associated with tyrosine kinases: JAKs (associated enzymes)
3) latent gene regulatory activaed by JAKs

Front 51

receptor guanylyl cyclases

Back 51

small family of receptors that bind specific peptides activating the catalytic domain of the cytoplasmic portion of the receptor, stimulating the production of cGMP
-cGMP activates a

Front 52

cGMP activates a ____

Back 52

cGMP-dependent protein kinase that phosphorylates serines & threonines on specific proteins involved in regulating these physiological responses