Lecture 5: Controlling cells Flashcards

1
Q

What components are needed to process signals?

A

signalling:
- signals
- membrane
- intracellular effector s

Gene expression:

  • transcription factors
  • Histones Chromatin remodelling factors
  • leads to state change (one expression change)
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2
Q

cell signalling (communication) is critical for

A

normal development, and function

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3
Q

cells have evolved several signalling mechanisms to allow cells to

A

communicate with each other

-these mechanisms are highly conserved and used multiple times in a animals life

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4
Q

the general model of cellular signalling

A

1) Reception of signal
2) transduction of a signal
3) cellular response

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5
Q

signal transduction:

A
  • receiving information into a cell

- acting on that information to make choices

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6
Q

signal transduction pathway:

A

Extracellular signals –> Signal transduction –> nucleus –> Protein expression –FEEDBACK TO NUCLEUS & SIGNAL TRANSDUCTION –> Response

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7
Q

Signalling cascades perform 5 crucial functions:

A
  1. TRANSUCE signal into molecular form that can stimulate response
  2. RELAY signal from point of reception to point of action in the cell
  3. AMPLIFY the received signal
  4. DISTRIBUTE the signal to influence several responses in parallel
  5. Each step is open to MODULATION by other signals
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8
Q

receptors relay signals via

A

…intracellular signalling pathways

  • individual cells respond to a certain set of signals for which they have receptors (specificity)
  • one cell may have 10 to 100,000 different receptors
  • many signals acting together can elicit different cellular responses - a complex network
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9
Q

many signalling proteins act as

A

molecular “switches”

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10
Q

a signalling molecule may induce

A

different responses in different cell types

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11
Q

do extracellular signals act slowly or rapidly?

A

Either

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12
Q

signalling via chemical signals can be in two forms of communications

A
  • direct (Gap junctions[animals], plasmodesmata [plants], interaction of cell-surface molecules
  • local (local signalling =paracrine signaling, synaptic signalling, or hormonal signalling)
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13
Q

two classes of extracellular signalling molecules

A

1) small hydrophobic molecules
- small enough or hydrophobic and pass through the membrane
- Directly activate intracellular receptors in the cytoplasm
or nucleus of target cell
2) Hydrophilic molecules
-Molecules too large or too hydrophilic to cross the plasma membrane
- rely on membrane receptors

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14
Q

examples of small hydrophobic molecules in extracellular signalling

A

1) Steroid hormones
- steroids structurally similar to cholesterol
- hydrophobic
- signals through intercellular receptor

2) Nitric Oxide (NO)
- NO is a chemically unstable gas
- NO is a small,uncharged molecule
- signals through cytoplasmic receptor

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15
Q

Cell surface receptors convert…

A

chemical signals –> electrical signals

  1. Ion channel opening (i.e. K+ channels in heart muscle cells)
  2. Membrane-bound enzymes (e.g. adenyl cyclase, phospholipase)
  3. G protein linked receptors
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16
Q

Enzyme-linked receptors fall into 3 categories:

A
  1. Receptor tyrosine kinases
  2. Cytokine receptors
  3. TGF-beta- type receptors
17
Q

receptor tyrosine kinases: ligands are

A

soluble or membrane-bound peptide or protein hormones (i.e. insulin, growth factors)

18
Q

Some receptor tyrosine kinases have been identified in studies of

A

human cancers - mutant forms send proliferated signals to cells in absence of signal

19
Q

receptor tyrosine kinases _____ themselves

A

autophoshorylate: phosphorylation of the kinase by itself.

20
Q

activation of a receptor tyrosine kinase stimulates

A

assembly of a signalling complex

21
Q

receptor tyrosine kinases activate

A

the G protein Ras

22
Q

Ras activates

A

a cascade of kinases called MAP-kinases

23
Q

receptor tyrosine kinases can activate the

A

PI-3-kinase-Akt pathway

24
Q

Activated Akt serves as a

A

survival signal for the cell & stimulates growth

25
Q

cytokines are ..

and control ..

A

are ..small secreted proteins
and control.. growth and differentiation of many types of tissue (i.e. induce information of different types of blood cells, interferons)

26
Q

cytokine receptors signals to the

A

nucleus in a direct pathway

27
Q

TGFbeta =

A

transforming growth factor beta

28
Q

TGFbeta receptor signalling

A
  • a number of related extracellular signalling molecules important during development
  • exert anti-proliferate signals to cells - loss of function can contribute to malignancy
29
Q

mutations in the TGFbeta receptor signalling pathway are often associated with

A

pancreatic cancers but also implicated in colon, liver and gastric tumours

30
Q

TGFbeta & BMP signalling

A

COMPETE

BMP = bone morphogenetic protein

31
Q

WNT signalling OFF state

A
  • Beta-catenin is associated with E-cadherin
  • Targeted phosphorylation by CK1 and GSK3beta leads to ubiquitination
  • Ubiquitination leads to breakdown
32
Q

WNT signalling ON state

A

-Wnts bind frizzled receptors.
-LRP5/6 brought into WNT/Frizzled (Fzd) complex
-LRP5/6/Wnt/Fzd activate Dishevelled (Dvl)
-Dvl displaces GSK3beta – prevents
- Beta-catenin destruction.
Beta-catenin is free to be translocated to nucleus to turn on target genes by displacing co- repressors from TCF/LEF

33
Q

NOTCH signalling

A
  • The Notch signaling pathway is a highly conserved cell signaling system present in most multicellular organisms.
  • works between adjacent cells
34
Q

examples of long range signalling

A

WNT, BMP etc

35
Q

How do we turn off signals:

A

Receptor signalling may be inactivated cha different mechanisms.

  • receptor sequestration
  • Receptor down-regulation
  • receptor inactivation
  • inactivation of signalling protein
  • production of inhibitory protein
36
Q

signalling pathways exhibit different degrees of complexity: low to high.
JAK-STAT, RTK, hormone, Notch

A

increasing complexity & increasing output diversity

  • hormone
  • notch
  • JAK-STAT
  • RTK
37
Q

signalling pathways exhibit a high degree of

A

interconnectedness

38
Q

signalling plays a crucial role in affecting

A

cellular decisions