Molecular Signaling Flashcards

1
Q

endocrine

A

signal transported in blood long-distance, long-lasting, freely diffuses

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2
Q

paracrine

A

signal diffuses to neighboring target cell of a different cell type, local signaling, short lived

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3
Q

autocrine

A

secreting cells express surface receptors for the signal

ex. interleukin 1, release to cells of same type or near by, common in chemokines

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4
Q

direct/juxtacrine

A

bind to signaling cell which then binds to receptor on the target cell

ex: heparin binding to epidermal growth factor

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5
Q

hydrophilic signaling

A

do not penetrate plasma membrane but interact with specific receptors at cell surface

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6
Q

examples of hydrophilic signaling

A

epinephrine, insulin, glucagon

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7
Q

signaling molecule for hydrophilic signaling

A

receptor complex initiates production of second messenger molecules insude cells

trigger downstream cellular repsonses

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8
Q

receptors involved in hydrophilic signaling

A

G protein-coupled receptors

receptor tyrosine kinase

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9
Q

lipophilic signals pass through the

A

plasma membrane of target cells

ex. steroid, thyroid, retinoids

bind to specific receptor proteins inside the cell

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10
Q

the signaling molecule for lipophilic signaling is

A

receptor complex that acts as a transcription factor

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11
Q

cytoplasmic receptors

A

inactive form complexed with HSP 90

hormone receptro complex translocates to nucleus where it binds to specific DNA sequence called hormone response element

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12
Q

nucleear receptors

A

already present in nucleus bound to DNa

the homrone allows for interactions with additional proteins and activate the complex

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13
Q

both cytoplasmic and nuclear receptors regulate

A

transcription of specific genes

long half lives (hours to days)

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14
Q

GPCR

A

structural motif

extracellular domain for signaling

transmembrane domain with 7 a-helices

intracellular domain-interacts with g proteins

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15
Q

GPCR signaling

A

trimer G protein with three subunits (aBy)

ligand binds receptor

conformational change

GPCR interacts with G protein

Receptor then acts as GEF-guanine exchange factors

inactive G protein has GDP, to be active, must exchange it for GTP

GTP-a separates from By and activates or inhibits effector molecule

effector molecule catalyzes reactions that produce secondary molecules

intrinsic GTPase activity of the G protein hydrolzes GTP to GDP to inactivate the G protein again

activation accelerated by GTPase ativating protein (GAP)

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16
Q

signal desensitization by

A

drop in hormone levels

decrease in adenylylyl cyclase-decreases cAMP-decreases PKA

17
Q

signal desensitization by

A

phosphodiesterase removinh cAMP/cGMP

18
Q

signal desensitiization by receptor sequestration and preceptor destruction

A

either by endosomes or endosomes and lysosomes as proteases

19
Q

Gs stimulates

A

adenylate cyclase

20
Q

Gt stimulates

A

stimulates cGMP phosphodiesterase

21
Q

Gi inhibits

A

adenylate cyclase

22
Q

Gq activates

A

phospholipase C

23
Q

GPCR with signaling via Gq, PLC, PKC (fig 7.5) and

A

book

24
Q

hydrolysis of cyclic nucleotides

A

enzymes hydrolyze cyclic nucletoides to regulate their cellular levels

cAMP phosphodiesterase hydrolyzes cAMP to AMP

  • cGMP phosphodiesterase: hydrolyzes cGMP to 5’GMP*
  • inhibitors of cGMP PDE increase concentration of cellular cGMP and prolongs its effects for a greater amount of time leading to smooth muscle relaxation and vasodilation resulting in erection (viagra, cialis)*

caffiene inhibits PDE leading to accumulation of cAMP, increasing heart rate

25
Q

inhibition of G proteins by bacterial toxins: Cholera

A

cholera toxin prevents the inactivation of Gsa

cholera illness by consumption of contaminated water

  • covalent modification of a subunit of Gs*
  • ADP ribosylation of Arg in Gs a decreases intrinsic GTPase activity*
  • Gsa remains active GTP bound form and continuously stimulates adenylate cyclase, resulting in overproduction of cAMP*
26
Q

Overabundance of cAMP in intestince causes

A

cell opens Cl channles and loss of water and electrolytes happens

cAMP activates the CFTR and secretes the Cl which leads to water secretion

27
Q

inhibition of G proteins by bacterial toxins: Pertussis

A
  • Pertussis toxin prevents the activation of Gia ADP ribosylation of Cys on Gia prevents actication and dissociation of a subunit from teh trimeric G protein complex*
  • Less inhibition of AC and hence overproduction of cAMP*

in airway, pertussis causes loss of fluids and mucous secretion increase presents as whooping cough

28
Q

nitric oxide diffuses to

A

neighboring muscle and activates guanylate cyclase, leading to production of cGMP

cGMP produced from activated guanylate cyclase resulting in smooth muscle relaxation and vasodilation

NTG and other nitrates decompose to form NO and help lower BP

should not take cGMP PDE inhibitors (erectile dysfunction drugs) with NO because it can cause extreme vasodilation and fatal BP drop

29
Q

histamine and antihistamine

A

histamines are made from histidine which is a ligand that binds to four histamine GPCRs

antihistamines are lipophilic compounds that block the effects of histamine to the H1 GPCR

30
Q

RTK motif

A

extracellular domain with signaling molecules

single helix

intracellular domain posses tyrosine kinase activity

31
Q

RTK signaling

A

signal binds to ECD inducing a conformational change

tyrosine is autophosphorylated

phosphotyrosine recognized by adapter and docking p (SH2 domain of grb2)

triggers phosphorylation of protein targets leading to alteration in gene transcription and protein activity
-this is either ras dependent or ras independent

RTK signaling is terminated by several ways (degradation, endocytosis, lysosomal degradation, accelerated ras inactivation, dephosphorylation

32
Q

ras dependent signaling

A

facilitated by mitogen activated protein kinase (MAPK) faily

33
Q

ras independent singaling

A

facilitated by a different kinase (NOT MAPK)

34
Q

many signaling molecules are

A

protooncogenes that can mutate into oncogenes

35
Q

Monomeric G proteins

A

small g protein part of RAS familt

very differnt from the trimeric G proteins in GPCR

monomeric G proteins have a single polypeptide chain

control a diverse process: cell proliferation, intracellular vesicular traffic, survival, apoptosis, shape, transport

have intrinsic GTPase activity, mutations here can cause cancer

include RAS, RAB, RHO, RAN

36
Q

RTKs in cancer

A

excessive signaling from mutated/overexpressed RTKs associated with cacner

RTKs are the target of pharm. inhibitors

breast cancer drug herceptin targets HER2 in the EGF-binding RTKs

37
Q

Ras in cancer

A

mutant forms of ras or GEFs or GAPs implicated in many cancers

half of lung and colon and 90% of pancreatic cacners associated with activating point mutations in RAS

mutations decrease GTPase activity and lock it in active GTP-bound state

ex. neurofibromatisis caused by inactivating mutation in NF-1 gene which encodes GAP for RAS. here RAS uncontrollably activated pathways for nerve tissue growth