Receptors and Cell Signaling & Cell Cycle, Apoptosis, and Cancer Flashcards Preview

MCM I > Receptors and Cell Signaling & Cell Cycle, Apoptosis, and Cancer > Flashcards

Flashcards in Receptors and Cell Signaling & Cell Cycle, Apoptosis, and Cancer Deck (37):
1

Endocrine Signaling

Long distant signaling; goes to distant target cells
Signal --> bloodstream
Long lasting effects
Signal freely diffuses

2

Paracrine signaling

Acts locally
Short lived signal
Ex. NT

3

Autocrine signaling

Cells responds to signals that they themselves released
Cell secretes signal that feeds back on binds to own receptor
Ex. Growth factors in cancer cells

4

Direct/Juxtacrine cell signaling

Where signal is brought directly to target cell
Ex. Immune cells
Ag-presenting cells to T cells

5

Lipophillic molecules

Long half-lives (hrs - days)
Often taken daily
Bind to intracellular receptors

Ex. Ethinyl estradiol

6

Hydrophillic molecules

Short half-lives (sec - min)
Administered when needed
Bind to extracellular receptors --> signal transduction
1) Change in activity/function of enzymes (fast)
2) Change in amounts of protein by change in expression of genes (slow)

Ex. Epinephrine

7

Cholera toxin

Prevents activation of Gs-alpha subunit
-Covalently modifies (via ADP ribosylation) the alpha subunit of Gs.
-ADP ribosylation of an arginine residue on Gs-alpha decreases its intrinsic GTPase activity
-elevated cAMP --> opening Cl- channels --> loss of water and electrolytes

8

Pertussis toxin

Prevent activation of Gi-alpha subunit
-ADP ribosylation of a cysteine residue on Gi-protein prevents activation and dissociation of its subunit from the trimeric G protein
-Result: less inhibition of adenylate cyclase and overproduction of cAMP
-In airway epithelial cells, pertussis toxin causes loss of fluids and excessive mucous secretion --> whooping cough

9

Desensitization of signal

Remove signaling molecule: phosphodiesterases will remove cAMP/cGMP

Receptor sequestration: endosome

Receptor desctruction: endosomes + lysosomes (proteases)

10

GRK

G protein receptor kinases phosphorylate receptor and recruits arrestin

Arrestin binds to 3rd loop and prevents Ga from interacting with 3rd loop
Result: G-alpha GDP doesn't get converted to G-alpha GTP

11

Phosphodiesterases

Breakdown cAMP and cGMP

12

Oncogenes

Promote cell proliferation
src
erb
ras

Inhibit apotosis
bcl-2

13

Tumor suppressor genes

Inhibit cell proliferation
apc
rb

Promote apotosis
p53
BRCA1
BRCA2

14

Cyclins in G1

Cyclin D - CDKs 4 and 6

15

Cyclins in G1 --> S transition

Cyclin E - CDK2

16

Cyclins in S

Cyclin A - CDK2 activation to induce enzymes necessary for DNA synthesis

17

Mitosis

Cyclin A -CDK1 and Cyclin B -CDK1

18

CIP/KIP family of CKIs

CKIs bind to G1 and S phase cyclin-CDK complexes to activate the kinase activity of CDK
-Eventually degraded

19

INK4 family of CKIs

Bind specifically to G1 CDKs
-Prevents them from associating with cyclin D

20

Wee1 Kinase

Phosphorylates roof site of CDK to inhibit cyclin and CDK association

Inactivates CDK

21

Cdc25 phosphatase

Dephosphorylates the roof site of CDK to allow activation and association with cyclin.

Activates CDK

22

APC/C

Targets S-cyclins and M-cyclins
Cyclins destroyed
Inactivates most CDKs
CDKs dephosphorylated
Needed for cell to move to anaphase
-Must get rid of s-cyclin and m-cyclin

23

Cdc20

Activates APC/C

24

p53

Tumor suppressor gene
TF
Stabilized by phosphorylation

Active p53 leads to transcription of CKI (p21)
p21 binds and inactivates cyclin-CDK complexes --> cell cycle arrest

25

MDM2

Keeps p53 inactive
An E3 ubiquitin ligase that keeps p53 inactive through degradation

26

p21

p53 --> transcription of p21
p21 binds and inactivates cyclin-CDK complexes --> cell cycle arrest

Cyclin E-CDK2 (G1 --> S phase transition) and Cyclin A-CDK2 (S phase transition) targets of p21

27

BAX

Stim. release of cyt C from Mito
Activates intrinsic pathway of apotosis

28

Bcl-2

Inhibits cyt C release from Mito
Inhibits intrinsic pathway of apotosis
Inhibits aggregation of APAF-1 --> inhibition of Caspase-9

29

Ras

Proto-oncogene
Point mutation at codon 12 gly --> val

Result: Ras oncoprotein occurs ~25% cancers

30

HER2

Proto-oncogene
Member of the family of EGF receptors (RTKS)
Point mutation val --> gln

Result: Oncoprotein NEU observed in some breast cancers

Amplification
Result: overexpression of HER2 & observed in many breast cancers

31

EGF receptor

Proto-oncogene
Deletion in part of a gene

Result: oncoprotein EGFRvIII lacks the extracellular ligand-binding domain and constitutively signals in the absence of ligand
Glioblastoma

32

N-Myc

Proto-oncogene
Amplification

Result: Elevated levels N-Myc transcription factor observed in neuroblastoma

33

c-Myc

Proto-oncogene
Chromosomal translocation

Reciprocal translocation b/w chr 8 and 14

Result: MYC TF overexpressed because translocation puts c-Myc under the influence of the immunoglobulin heavy-chain gene enhancer

Observed in Burkitt lymphoma

34

ABL

Proto-oncogene
Translocation b/w chr 9 and 22, which generates a derivative of chromosome 22 known as Philadelphia chromosome

Result: Generates the BCR-ABL fusion oncoprotein (an unregulated protein tyrosine kinase) because the translocation creates a BCR-ABL fusion gene

Creates chromic myelogenous leukemia (CML)

35

Herceptin

Inhibits HER2 receptor & NEU

36

Erbitux

Inhibits EGF receptor

37

Gleevec (imatinib)

Inhibits BCR-ABL fusion protein