Cell Signaling Molecules

Front 1

GAPs

Back 1

- GTPase Activating Proteins

- Assists in hydrolysis of GTP

Front 2

TGF ß

Back 2

- Transforming Growth Factor ß

- Binds to a certain class of serine-threonine kinase receptors

- Regulates... cell proliferation, programmed cell death, specialization of cells, key events in embryonic development

Front 3

GEF

Back 3

- Guanine Nucleotide Exchange Factor

- Removes GDP from active site for binding by GTP

Front 4

RGS

Back 4

- Regulators of G Protein Signaling

- Act as GAPs

Front 5

MAP Kinases

Back 5

- Mitogen Activated Protein Kinases

- Involved in Ras pathway

- Activated by MEK phosphorylation

- Activated when cells receive stimulus to grow and divide

- Functions: Phosphorylate transcription factors, Jun, Ets

Front 6

Epinephrine

Back 6

- (Adrenaline)

- Endocrine hormone

- Product of the adrenal gland

- Life span of a few seconds

- Target tissues: heart, liver

- Binds to adrenergic receptors

Front 7

GLUT4

Back 7

- Component of insulin signaling

- Glucose transporter protein

- Movement activated by Akt

- Movement from vesicles in cytosol to plasma membrane allows glucose uptake

Front 8

Insulin

Back 8

- Ligand for receptor tyrosine kinases

- Long lifespan

- Target tissues: liver and skeletal muscles

- Protein hormone

- Ultimately reduces blood sugar levels

Front 9

Smads

Back 9

- Class of proteins

- R-Smads: "receptor-regulated" Smads

- C-Smads (Smad4): Form multi protein complexes with phosphorylated R-Smads

- I-Smads: "Inhibitor" Smads

- Regulate gene expression

- Activated as a result of growth factor binding (e.g., TGF ß) to serine-threonine receptor kinases

- Signals terminated when R-smad is degraded or moves back to cytosol

Front 10

Akt

Back 10

- Protein Kinase B

- Role in insulin signalling pathway

- PIP3 binds to Akt

- Leads to movement of glucose transporter to the membrane

Front 11

PI 3-kinase

Back 11

- Phosphatidylinositol 3-kinase

- Can be activated by receptor tyrosine kinases

- Phosphorylates plasma membrane phospholipid phophatidylinositol

- Regulates cell growth and movement

- Role in insulin signalling (catalyzes conversion of PIP2 to PIP3)

Front 12

IRS-1

Back 12

- Insulin Receptor Susbtrate 1

- Protein in insulin pathway

- Phosphorylated by ß sun bin as a result of insulin binding

- Can stimulate 2 pathways:

1) Recruitment of GRB2 to activate Ras pathway

2) Bind PI 3-kinase

Front 13

PTEN

Back 13

- Regulator of insulin signalling

- Enzyme that acts to oppose PI 3-kinase

- Removes phosphate group from PIP3

- Prevents activation of Akt

Front 14

GRKs

Back 14

- G protein-linked receptor kinases

- Regulate G protein-linked receptors by desensitizing

- Phosphorylation of specific amino acids in the G protein-linked receptor's cytosolic domain

Front 15

Ras

Back 15

- From Rat Sarcoma

- Single subunit

- Active state: bound to GTP

- Ultimately activates expression of genes involved in growth or development

- Activated by Sos

- Activates protein kinase

Front 16

Sos

Back 16

- "Son of Sevenless"

- Guanine-nucleotide exchange factor (GEF)

- Activates Ras by converting GDP to GTP ("on switch")

- Binds indirectly to the receptor tyrosine kinase through GRB2 to become active

Front 17

GRB2

Back 17

- Forms complex with Sos to bind to receptor tyrosine kinase to activate Sos

- Contains an SH2 domain

Front 18

EGF

Back 18

- Epidermal Growth Factor

- Ligand for the Ras pathway

- Bind to receptor tyrosine kinases

Front 19

Raf

Back 19

- Protein kinase

- First protein involved in Ras pathway

- When activated, phosphorylates serine and threonine residues in protein, MEK

Front 20

MEK

Back 20

- Protein Kinase

- Involved in Ras pathway

- Activated by phosphorylation by Raf

- Phosphorylates serine and threonine residues in MAPKs

Front 21

Ets

Back 21

- Family of transcription factors

- Regulate gene expression

- Phosphorylated by MAPKs in the Ras pathway

Front 22

Jun

Back 22

- Component of the AP-1 transcription factor

- Phosphorylated by MAPKs in the Ras pathway

- Regulate gene expression of proteins whose products are needed for cells to grow and divide

Front 23

PIP2

Back 23

- Phosphatidylinositol-4,5-bisphosphate

- One of the phospholipids present in the membrane

- Broken down by the enzyme phospholipase C to IP3 and DAG

Front 24

IP3

Back 24

- Releases calcium from intracellular stores in the ER to the cytosol

- Produced when phopholipase C cleaves PIP2 to form IP3 and DAG

Front 25

DAG

Back 25

- Diacylglycerol

- Produced when phospholipase C cleaves PIP2 to form IP3 and DAG

- Remains in membrane upon production

Front 26

Phospholipase C (PLC)

Back 26

Phospholipase Cß:

- Activation can lead to production of IP3 and DAG

- Activated by GPCRs

Phospholipase Cɣ:

- Contains SH2 domain

- Activated by receptor tyrosine kinase

- Activation can lead to production of IP3 and DAG

Front 27

cAMP

Back 27

- Cyclic AMP

- Second messenger

- Allosteric regulator of protein kinase A (stimulates activity)

Front 28

Calmodulin

Back 28

- Calcium Modulating Protein

- "Arm" with "hand" at each end

- "Hands" bind to Ca2+

- Binding to calcium induces a change in conformation

- Binding to a protein can alter function

Front 29

Erk

Back 29

-

Front 30

PDGF

Back 30

- Plateletd-derived Growth Factor

- Associates with receptor tyrosine kinase

Front 31

BMP

Back 31

- Bone Morphogenic Protein

- Ligand for Smad signalling

Front 32

PKA

Back 32

- Protein Kinase A

- Phosphorylates amino acids on G protein-linked receptors to inhibit activity

- Involved in desensitization

- Catalyzes phosphorylation of a variety of proteins

Front 33

CRE

Back 33

- Cyclic AMP response element

- DNA sequences

- Located adjacent to genes whose transcription is induced by cAMP

Front 34

CBP

Back 34

- CREB Binding Protein

- Transcriptional co-activator

- Recruited by CREB upon its phosphorylation

- Catalyzes histone acetylation (loosens nucleosome packing and interacts with RNA polymerase to facilitate assembly of the transcription machinery at nearby gene promoters)

Front 35

CREB

Back 35

- CRE Binding Protein

- Transcription factor

- Binds to CRE DNA sequences to increase or decrease the transcription of downstream genes

Front 36

Calcium Ionophores

Back 36

- Cause membranes to become permeable to calcium, allowing entry to the cytosol from the ER and extracellular stores and mimicking the effect of IP3

Front 37

Adenylate Cyclase

Back 37

- Converts ATP to cAMP

- cAMP does not phosphorylate target proteins