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Cell Physio > Cell SignalingII > Flashcards

Cell SignalingII Flashcards

1
Q

Protein kinase associated membrane receptors

A
  • Membrane receptors that directly transmit signals via phosphorylation of Intracellular protein targets(protein kinase receptor)
  • The receptor is a kinase(activated upon ligand binding)
  • 2 main types(receptor tyrosine kinase,receptor serine/threonine kinase
  • many growth factors bind to protein kinase receptors
  • important roles in cell proliferation,growth, and cancer
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2
Q

Receptor Tyrosine kinase examples

A
  • insulin receptor
  • insuline-like growth factor-1(IGF-1)receptor
  • nerve growth factor receptor
  • epidermal growth factor(EFG) receptor
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3
Q

Structure of receptor tyrosine kinase

A

-single polypeptide chain(may oligomerize upon ligand binding)
-single transmembrane domain
Extracellular portion-contain ligand binding domain
Intracellular portion-(tyrosine kinase domain, multiple tyrosine residues that can be autophosphorylated)

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4
Q

Epidermal growth factor(EFG) receptor

A
  • EFG binding site on Extracellular portion
  • single transmembrane domain (single pass,synthesized at RER,ERSS and single internal stop transfer(c-terminus is in cytoplasm)
  • tyrosine kinase domain and multiple tyrosine residues(at cytosolic tail) on the Intracellular portion
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5
Q

Insulin like growth factor 1(IGF)

A
  • 2 cross linked dimers(alpha and beta subunits)
  • IGF-1 binding site on Extracellular portion
  • single transmembrane domain for each dimer(ERSS and single internal stop transfer)
  • tyrosine kinase domain and multiple tyrosine residues on the Intracellular portion
  • encoded by a single gene and a single mRNA(the initial polypeptide is then glycosylated and cleaved into the subunits)
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6
Q

EGF receptor activation function

A

Stimulate the growth repair, and proliferation of epithelial and mesenchymal cells and tissues

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7
Q

EGF(ligand) binding results in?

A
  1. Receptor aggregation(dimer)
  2. the tyrosine kinases of the 2 receptors phosphorylate the tyrosine residues on the opposing receptor(autophosphorylation to form phosphotyrosine
  3. following authophosphorylation,the cytosolic portion undergoes a conformational change that results in interactions with additional cytosolic signaling proteins
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8
Q

EGF receptor signaling

A

1.the ligand(EGF) bind to the receptor(EGF receptor) and activates via dimerization and authophosphorylation
2.following activation, proteins that bind to phosphotyrosine can then interact with the receptor (these proteins have SH2 domains that binds phosphotyrosine)
GRB2-growth factor receptor-bound protein 2-activated Ras
3. Binds GTP via SOS
4.PLCgamma-to form DAG and IP3 from PIP2
5-7 following Ras activation(GTP binding)Ras initiates a series of phosphorylation steps
8.Ets and jun(along with fos)then promotes the expression of gene related to growth and mitosis
9.following signal termination,Ras is inactivated by GAPs(GTPase activating proteins)
The GAP facilitates GTP hydrolysis by Ras
Thus Ras is now bound to GDP and is inactive

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9
Q

Following Ras activation(GTP binding),Ras initiates a series of phosphorylation steps

A

A)raf (mitogen activated protein kinase(3) MAPKKK.
B)mek (MAPKK)
C)MAPK
D)Ets(E twenty six,family of transcription factor
E)jun(early response transcription factor)

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10
Q

Insulin stimulates what?explain

A
  • stimulates glucose uptake into cells.
  • The Insulin receptor (RTK), upon ligand binding and autophosphorylation, activates IRS-1 (insulin receptor substrate-1) via phosphorylation
  • IRS-1 in turn activates PI3K, Akt (protein kinase B), → → elevation in glucose transporters in cell membrane via regulated secretion
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11
Q

IGF stimulates what?

A

cell growth via activation of IRS-1, PI3K, Akt (protein kinase B), mTor, ribosomal synthesis and activity

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12
Q

Differs RTKs activate..

A

Different cellular signaling pathways

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13
Q

Receptor Serine Threonine Kinases (RSTK)

A

-Some growth factors utilize RSTKs to initiate intracellular signals
Ex:TGFb family of receptors
-Generally involve 2 types of receptors that function together
Type I and type II receptors (cooperatively bind the ligand, TGF or similar molecules like myostatin)
Both receptors are serine/threonine kinases
Send intracellular signals via the phosphorylation of R-Smad (receptor regulated Smad)
-R-Smads are a family of transcription factors

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14
Q

TGFb family of receptors

A

Regulate a wide variety of cellular functions

Proliferation, apoptosis, cellular development & differentiation

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15
Q

Process of thereonine/serine

A

-Prior to binding the ligand, the receptors (type I and II) are located individually at the cell surface(1. In the absence of TGF beta, the type I and II receptors TGFbeta are not clustered or phosphorylated. R-Smads and Smad4 are in cytosol.
-2. Binding of TGFbeta results in clustering of type I and II receptors, followed by phosphorylation of type I receptors by type II receptors
3-the activated type I receptor bind a complex of an anchoring protein and an R-Smad, resulting in R-Smad phosphorylation
-The phososphorylated R-Smad interacts with Smad-4 proteins and is translocated to the nucleus where it can influence gene expression in association with other transcription factors and co-regulators

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16
Q

Myostatin

A
  • TGFb family member
  • Acts as a muscle growth inhibitor, secreted by muscle
  • Knock out myostatin → elevated muscle growth.
  • Occurs naturally:
    1. Double muscled cattle
    2. Mice
    3. Dogs
    4. Human
17
Q

Myostatin receptor

A
  • activin receptor (RSTK)

- type I and II

18
Q

Functions of myostatin

A
  1. Myostatin binds to the receptor
  2. Causes phosphorylation of type I and then recruitment & phosphorylation of R-Smad
  3. R-Smad enters nucleus with Smad-4
  4. Changes in gene expression → suppress growth
19
Q

How do hormones exert such a wide variety of effect?

A

Epinephrine

20
Q

Epinephrine(adrenaline)

A

Hormone that stimulates a variety of cellular effects in different tissues (fight or flight response)

21
Q

How can epinephrine have such a diverse array of functions?

A
  1. different receptors subtypes in different tissues
  2. linked to different G-protein
  3. and linked to different Intracellular signaling pathways and down stream targets
22
Q

Smooth muscle response to what?

A

Adrenegic stimulation

23
Q

Respiratory passage ways

A
  • trachea, bronchi, bronchioles
  • Have b2-adrenergic receptors
  • Activate Gs→ ↑adenylyl cyclase activity, → ↑cAMP, → smooth muscle relaxation→ airway dilation (bronchodilation).
24
Q

Vasculature of (arteries & arterioles) skin, GI, kidney, brain

A
  • Have a1-adrenergic receptors
  • Activate Gq→ ↑PLC activity, → ↑IP3, → ↑ cytosolic [Ca2+] → smooth muscle contraction → vessel constriction → decreased blood flow.
25
Q

•Vasculature (arteries & arterioles) of skeletal & cardiac muscle

A
  • Have b2-adrenergic receptors

- Activate Gs→ ↑adenylyl cyclase activity, → ↑cAMP, → smooth muscle relaxation→ vessel dilation → increased blood flow.

26
Q

Epinephrine effects on glycogen metabolism

A

1-cAMP bind to and activates protein kinase A
2-protein kinase A phosphorylates phosphorylase and activating it
3-active phosphorylase kinase phosphorylate phosphorylaseb, converting it to phosphorylase a, the active form of the enzyme
4-phosphorylase a catalyzes cleavage of a terminal glucose from glycogen as glucose 1-phosphate

27
Q

Adrenergic agonists (sympathomimetics)

A
  • Phenylephrine (nasal decongestant)
  • Ephedrine (pseudoephedrine)
  • Clenbuterol, salbutamol (albuterol), metaproterenol, ractopamine (asthma treatments)
  • propranolol
28
Q

Phenylephrine (nasal decongestant)

A
  • alpha1-adrenergic agonist (stimulates PLC and smooth muscle contraction)
  • vasoconstriction of nasal blood vessels, results in reduced blood flow to the nasal mucosa, relieves swelling of nasal mucosa
29
Q

Ephedrine (pseudoephedrine

A
  • Same as phenyleprine, but also induces the release of noradrenaline
  • Stimulant actions (stimulates heart rate) result from direct and indirect activation of α- and β-adrenergic receptors (via noradrenaline release)
  • Actions on b-adrenergic receptors allow for airway dilation (bronchodilation)
  • Also used illicitly to manufacture methamphetamines
30
Q

Clenbuterol, salbutamol (albuterol), metaproterenol, ractopamine (asthma treatments)

A
  • b2-adrenergic agonists (stimulate adenylyl cyclase and smooth muscle relaxation), allow for airway dilation (bronchodilation)
  • Also used to increase muscle mass, somehow activate the IGF-1 growth related pathway (at Akt)
31
Q

Propranolol

A
  • Blocks the b receptors
  • Used for treating high blood pressure and heart pain (angina) and heart arrhythmia
  • Results in reduced blood pressure by
    1. Reducing heart rate
    2. Reducing the force of heart contractions

Cell Physio (5 decks)

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