White - Cell Communication 2 Flashcards

1
Q

What does PKA stand for and what does it do?

A

Protein Kinase A; it is the downstream target of cAMP that acts on target proteins

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2
Q

When GPCR attaches to G-alpha-q or G-alpha-o, what is the effector in this case?

A

Phospholipase C instead of adenylyl cyclase

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3
Q

What does phospholipase C do?

A

Cleaves PIP2 which produces IP3 and DAG 2nd messengers

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4
Q

What is the function of IP3?

A

Releases Ca2+ from the ER by binding to an IP3-gated Ca2+ channel and triggers opening

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5
Q

What is the function of DAG?

A

Binds to protein kinase C along with Ca2+, causing a conformational change and activating PKC

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6
Q

What is the function of PKC?

A

Phosphorylates a variety of membrane and cytoplasmic substrates

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7
Q

Calmodulin

A

Protein that calcium binds to and can bind and activate other proteins to activate their functions

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8
Q

CaM Kinase II

A

Calmodulin-dependent kinase; can phosphorylate transcription factors so they can bind to DNA for transcription

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9
Q

Receptor Tyrosine Kinases (RTKs)

A

Play important role in signal transduction; enzyme linked receptors; enzymatic domain is in the cytoplasmic tail of the integral membrane protein; binds growth factor through extracellular domain

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10
Q

Growth Factors

A

Proteins released by cells to promote growth of other cells; cause cells to proliferate and grow in cell culture

Examples: Epidermal Growth Factor (EGF), Platelet Derived Growth Factor (PDGF), Nerve Growth Factor (NGF), Fibroblast Growth Factor (FGF), Insulin-like Growth Factor 1 (IGF-1)

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11
Q

Components of RTKs

A

Extracellular domain, transmembrane domain, cytoplasmic domain (transmits signal through tyrosine kinase domain); adds phosphate to tyrosine on proteins

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12
Q

RTK Activation

A
  1. Ligand binding to this receptor causes a conformational change that induces dimerization of two receptor monomers
  2. Autophosphorylation occurs
  3. This causes the receptor to act as a scaffold to recruit other proteins to the plasma membrane
  4. Receptor does NOT bind to G protein but to proteins with a domain called the SH2 domain, which binds to phosphotyrosine, such as Grb2
  5. Grb 2 also has SH3 domain that binds to prolines in SOS (Son of Sevenless), which then binds to Ras (small monomeric G protein - small GTPase)
  6. Ras binds Raf which initiates MAP Kinase Cascade
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13
Q

What is SOS?

A

A GEF that exchanges GDP for GTP on Ras

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14
Q

Ras

A

First discovered human oncogene; plays crucial role in cell division and a frequent mutation in cancer

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15
Q

What is MAP Kinase and what does it do?

A

Mitogen Activated Protein Kinase; plays a role in cell proliferation

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16
Q

MAP Kinase Cascade

A

Ras initiates MAP kinase cascade–> MAP kinase kinase kinase (Raf)–> MAP kinase kinase (Mek)–> MAP kinase (ERK)–> nucleus–> increased gene transcription–> uncontrolled cell division (cancer) if unchecked

17
Q

Signal Transduction Process

A

Ligand–> high affinity receptors–> intracellular signal proteins–> effector proteins–> altered gene expression

18
Q

JAK-STAT Receptors

A

More direct route for impacting transcription

19
Q

JAK-STAT Receptor Process

A
  1. Ligand binds to receptor, receptors dimerize, then bind JAKs (Janus Kinases)
    2a. JAKs phosphorylate each other
    2b. JAKs phosphorylate receptor
  2. Receptor binds and phosphorylates STATs (signal transducer and activators of transcription proteins)
  3. STATs separate from receptors, dimerize and enters nucleus - binds to DNA and causes transcription of target genes

Erythropoeitin employs JAK-STAT to initiate signaling

20
Q

R-Smad

A

Receptor specific Smad

21
Q

Co-Smad

A

Common Smad

22
Q

Serine-threonine Receptor and Smad Process

A
  1. Activated receptor (by phodphorylation) binds to R-Smad and phosphorylates R-Smad
  2. R-Smad binds to Co-Smad and moves into nucleus to impact transcription of target genes

Example: Iron metabolism through hormone called hepcidin

23
Q

Hereditary Hemochromatosis

A

Uncontrollable iron absorption that leads to iron overloading; toxic levels of iron get deposited in organs causing end-organ disease; treatment is challenging due to patient compliance; most common autosomal recessive disease in man (1/250)

24
Q

DMT1

A

Absorbs iron into intestinal cells

25
Q

Ferroportin

A

Moves iron out of intestinal cells and into blood

26
Q

Hepcidin

A

25 aa protein made in the liver with action in the intestine; regulator of iron homeostasis by binding to ferroportin (hepcidin receptor); hepcidin binding causes internalization of ferroportin which is destroyed by proteolysis

27
Q

Relationship between Hepcidin and Ferroportin

A

Inverse; REPLETED iron causes an increase in hepcidin expression and decreased levels of ferroportin

DEPLETED iron causes a decrease in hepcidin expression and increased levels of ferroportin