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Signal transduction > signal transdcution > Flashcards

signal transdcution Flashcards

1
Q

What are MAP Kinases

A

serine/threonine kinases involved in regulation of many cell processes. (proliferation,apoptosi)

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2
Q

which is the SH2 domain protein in map K

A

GRB- docks onto the tyrosine residues

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3
Q

core kinase in Map K

A

Ras

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4
Q

signalling molecule-MAP K

A

Growth factor e.g IGF 1 , EGF

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5
Q

What is the function of SOS

A

Guanine nucleotide exchange factor for RAS

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6
Q

what is the pathway of insulin?

A

Still tyrosine kinase but a special type

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7
Q

Pathway of insulin

A
  1. Insulin binds to alpha
  2. Dimerises - the b subunits have kinase activity its heterotetrameric 2 a and 2 b which are transmembrane
  3. Autophosphorylation
  4. Phosphorylates IRS1
  5. PI3K (phosphoinosittid 3 kinase)
  6. Pip 2 - Pip 3 -PDK1 (enzyme)- AKT/protein kinase B. (enzyme)
  7. AKT phosphorylates inhibitory proteinAS160 which usually prevent GLUT 4. Also phosphorylates GSK3 which is an inhibitor of glycogen synthase.
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8
Q

The role of insulin in signal transduction

A

Has a mitogenic function (MAP K)

and also pathway is metabolic effect (PI3K)

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9
Q

what kind of molecules are chemical messengers usually?

A

hydrophilic only 4 are hydrophobic

  • steroid hormones
  • active vitamins D and A
  • Thyroid hormones
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10
Q

what mechanism do the hormones produced by the hypothalamus work with

A

Phospholipase C

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11
Q

relationship between PPP and Insulin

A

insulin activates PPP (anabolic)

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12
Q

GLUT 4 tissues

A

adipose, muscle, heart

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13
Q

GLUT 1

A

all cells, RBC - Insulin Independant

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14
Q

GLUT 3

A

brain, neurons, sperm. function in (hypo)
insulin indwpendant
high affinity, low KM

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15
Q

Explain MAP K

A
  1. ligand binds
  2. Dimerisation
  3. Autophosphorlation
  4. GRB 2 docks
  5. SOS binds
  6. RAS activated
  7. Kinase reaction
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16
Q

Glut 5

A

enterocytes of small intestine for the uptake of fructurse

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17
Q

GLUT 2

A

pancreas, liver, small intestine - (HYPER) low affinity and high KM -insulin independant

18
Q

which pathway is associated with TYRK

A

JACK STAT- growth hormones

19
Q

what are the molecules trigger JACK STAT

A

prolactin, GH, cytokines, INF

20
Q

IL-6

A

pro inflammatory cytokine, associated with hepicidin which decreases iron levels by stopping ferroportin. Hepcidin increases when IL -6 is present. Hepcidin blocks fe release from liver and SI

21
Q

JACK STAT

A
  • cytokines and GH
  • intracellular part of receptor associated with Jack (janus kinase)
  • signal binds and the jacks phosphorylate each other
  • Jacks phosphorylate Tyr
  • causes STAT (TF) to bind to the Tyr
  • JACK phosphorylates STAT
  • STAT dissociates from receptor goes to nucleus binds ta response elements and activates gene transcription
22
Q

Receptors with serine/threonine kinase activity

A

TGF -B receptors (transforming growth factors)

TGF receptor is complex, has 2 different receptor subunits. first 1 type 2 gets activated by the signalling molecule (TGF) then activates type 1 by phosphorylation at a ser residue.

type 1 binds to Smad (R-smad) which it phosphorylates at ser. R-smad dissociates from receptor and forms complex with co-smad. smad complex goes to nucleus to affect transcription.

Smads are gene specific TF’S

TGF is a hormone/cytokine involved in tissue repair, immune regulation , cell proliferation and bone morphogenic proteins (BMPS)

23
Q

what does associeted TYR kinase mean

A

The receptor itself has no intrinsic kinase activity but binds the the tyrosine kinase JACK

24
Q

Non receptor serine/threonine kinases

A

These are several serine/threonine protein kinases that are responsible for phosphorylating a variety of intracellular proteins on ser/thre residues. the most important are PK C A G

25
Q

mtor

A

ser/thr kinase regulates autophagy, proliferation, protein synthesis transcriptpm. coded for by FRAP 1 gene. forms 2 different complexes. rapamycin is a bacterial toxin that inhibits mtor by binding to its intracellular receptor FKBP12

mtor integrates the signal pathways of insulin, growth factors (iGF 1/2_

26
Q

PKG

A

directly stimulates

  1. synthesis of nO
  2. soluble intracellular Gunayl cyclase

INHIBITS phosphodiesterasde 5 - which selectively cleaves cgmp

PKG also modulates the PKG also modulates the intracellular concentration of intracellular concentration of
Са2+, which is a key ion for activity of , which is a key ion for activity of ( eNOS) and nNOS

27
Q

NOS pathway

A
  1. stimulate muscle with ACH
  2. Ativates ca dependant NOS synthase
  3. gas so diffuses to muscle and you have soluable guanyl cyclase there. binds to it, turns GTP-CGMP-PKC G
  4. relaxation of smooth muscle by activation of myosin light chain phospahatse
28
Q

PTEN

A

is a phosphatase which dephospharataltes PIP 3 thus inhibiting the PI3K pathway. its acts as a tumour supressor gene.

29
Q

what is the signalling molecule for PI3K

A

insulin, growth factors like a PDGF,EGF

30
Q

natriuretic peptide and receptors

A

It relaeases NA in urine

3 receptors

NPRA
NPRB
NPRAC- g protein linked and is a clearance receptor that internalises and destroys the ligand

31
Q

which is the aa precursor for nO

A

arginine

32
Q

plasma membrane receptors

A
  1. associated with ion channels
  2. associated with G proteins
  3. with intracellular domains with enzymatic activity
    - tk activity
    - tyrosine phosphatase
    - serine/thr activity
    - gunaylate cyclase activity
  4. death receptors
  5. integrins
33
Q

G proteins

A

so called as they bind to guanine nucleotides
heterotrimeric
Receptor spans the membrane 7 times
in its inactive state GS a has GDP bound
when ligand binds causes a conformational change replacement. the a subunit and GTP dissociate to go and activate adenylate cyclase

  • ATP—-CAMP—PKA
  • for response to stop GTP will be hydrolysed by GTPASE T then a will rejoin others.
34
Q

example of g protein

A

adrenaline

35
Q

different types of g proteins

A
  1. GS a-increases camp
  2. GI a- decreases camp
  3. GQ- involved in the ip3 pathway s
  4. Gt transducin
36
Q

g transducin

A

responsible for generating the signal int he rods of retina in response to light. it stimulates CGMP phosphodiesterase (break down)

37
Q

Regulation of glycogen synthase and phosphorylase

A

GS
:) - Insulin
:( glucagon and epinephrin

GP
:) glucagon and epinephrin
:( insulin

38
Q

G protein that regulate ion channels

A

Muscarinic ACH receptor in the heart .
linked to K channels
when ACH binds stimulates the G inhibitory unit
now b and gamma dissociate, bind to channels increasing k permeability, hyperpolarizing membrane and decreasing frequency of contractions

39
Q

rod cells

A

In dark, rod cells have a high level of cGMP which keeps the gates open (na)). When there is light activates opsin which cause sa displacement of gdp on a g protein called transdcucin. This activates Cgmp phosphodiesterase convertes CGMP-GMP leads to dissociation of cgmo from channeles leads them to close—–generate AP

40
Q

second messangers

A

They amplify the signal because more of it is produced compared to the first messenger. they are short lived intracellular signalling molecules. removal of the 2nd messenger terminates the response

the communication between cells

  1. Ca
  2. No/co
  3. CAMP/CGM[

Signal transduction (2 decks)

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