17. Cell signaling I. General concepts. Nuclear receptors. G-protein coupled receptors

Question 1

endocrie
hormone
autocrine

Answer 1

endocrine signaling
The type of intercellular signaling where signaling cells in endocrine glands secrete the
messenger molecules (hormones) into the blood stream, which carries the message to every part
of the body. This is how the signal molecules reach remote target cells that have the appropriate
receptor for them.
hormone
Extracellular signal molecules (primary messengers) secreted by endocrine glands that get into
the blood stream and thereby reach remote target cells and alter their functions by binding to
their receptors.
autocrine signaling
A type of signaling where the secreting/signaling cell and the target cell are the same, so the
same cell expresses the signal molecule (eg growth factor) and its receptor. It can be important
in coordinating groups of cells differentiating in the same direction during ontogenesis, but also
in the development of tumors.

Question 2

paracrine
juxtacrine

Answer 2

paracrine signaling
In this form of signaling, the secreted messenger molecule does not get into the blood stream,
rather, it reaches the target cells, maximally in a few mm distance, by diffusion through the
intercellular space. Its subtypes are: autocrine, juxtacrine, intracrine and synaptic signaling, and
directed secretion.
juxtacrine signaling
The subtype of paracrine signaling whereby the signal molecule is bound to the membrane of
the signaling cell (it is a cell surface molecule), and binds to its receptor which is in the
membrane of the neighboring cell, generating a contact-dependent signal. A typical example is
the delta/notch signaling route.

Question 3

intracellular receptor
nuclear receptors

Answer 3

intracellular receptors / nuclear receptors
Nuclear receptors are transcription factors located intracellularly. Their ligands are small
molecular weight, hydrophobic molecules. They bind to specific DNA sequences (HRE,
hormone response element) as homo- or as heterodimers. The homodimeric types are receptors
for steroid hormones, without ligand they are monomers in the cytosol, bound to an inhibitor,
and are dimerized and activated upon ligand binding, after dissociating from the inhibitor. The
heterodimeric types form dimers with RXR and bind to DNA even without a ligand, but in this
state they bind a co-repressor. Binding their ligand – e.g, retinoic acid, thyroxine, vitamin D –
causes the exchange of the co-repressor for a co-activator and promotion of gene transcription

Question 4

g protein couple receptor

Answer 4

G protein coupled receptors
Cell surface receptors without intrinsic (own) enzyme activity that bind ligands such as
glucagon and epinephrine. They have seven transmembrane alpha helices, hence their other
name, 7-transmembrane receptors, or serpentine receptors. They transmit the extracellular
signal to heterotrimeric G proteins. The activated G protein can activate or inhibit specific
effector proteins, such as adenilyl cyclase, phospholipase C, cGMP phosphodiesterase, or ion
channels.

Question 5

adenylyl cyclase

Answer 5

adenylyl cyclase – protein kinase A pathway
Adenylyl cyclase is membrane-bound enzyme activated by the trimeric G-protein Gs. It
catalyzes the formation of the second messenger cyclic AMP (cAMP) from ATP, e.g. upon the
effect of glucagon or epinephrine. Cyclic AMP is then degraded by cAMP phosphodiesterase.
The main role of cAMP is the activation of protein kinase A (PKA). PKA is a universal serinethreonine kinase phosphorylating targets for immediate (metabolic) cellular responses, e.g.
glycogen phosphorylase kinase in the liver or Ca channels in the heart, as well as transcription
factors like CREB.

Question 6

beta adrenergic receptor

Answer 6

Beta-adrenergic receptor
The beta-adrenergic receptor is a 7TM receptor (GPCR) which binds epinephrine and
norepinephrine and activates the stimulatory trimer G protein (Gs) and, through it, protein
kinase A. It can be found, for example, in the heart, which it stimulates to contract faster and
stronger, in the liver, where it increases glycogen breakdown, and in the lungs, where it causes
bronchodilation. These effects are characteristic for /nor/epinephrine released from the adrenal
gland’s medulla during a fight or flight reaction.

Question 7

kinase
secondary messengers

Answer 7

kinase
Enzymes that link the high energy phosphate group of ATP to OH residues of target molecules.
The process is phosphorylation, it is reversible: the removal of phosphate by phoshatases is
dephosphorylation. Of protein kinases serine and threonine kinases are specific for aliphatic
OH, eg. CamK, PKA, PKB, PKC, MAP3K, while tyrosine kinase phosphorylate aromatic OH,
eg. insulin receptor, EGF receptor, PDGF receptor, src and JAK; There are kinases with other
specific targets: PI3K is a lipid kinase; hexokinase is a carbohydrate kinase; timidin kinase is a
nucleoside kinase; there also are mixed specificity kinases.
second messenger
Molecules that relay the extracellular signal received by cell surface receptors to intracellular
target molecules. Second messengers are produced or released in specific reactions initiated by
the ligand bound receptors, and are consequently degraded or taken up into intracellular stores.
Examples are: Ca2+, IP3, DAG, cAMP.