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Cell signaling
Signal transduction
In mul<cellular organisms, cells with different func<ons
exchange a wide variety of signals.
The signal represents informa/on that is detected by
specific receptors and converted to a cellular response,
which always involves a chemical process. This
conversion of informa<on into a chemical change, signal
transduc<on, is a universal property of living cells.
Signal transduc/on is the process by which a chemical
or physical signal is transmiBed through a cell as a series
of molecular events, most commonly protein
phosphoryla<on catalyzed by protein kinases, which
ul<mately results in a cellular response.

Cell signaling
(Brief History)
In 1970, Mar<n Rodbell examined effects of glucagon on rat’s liver
cell membrane receptor

He revealed about guanosine triphosphate and s<mulated G-
protein role in cells metabolism

Nobel prize in physiology or

medicine, 1994

“for their discovery of G-
proteins and the role of these
proteins in signal transduc<on
in cells”

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Example:
Tumor cells: release growth factors for their own survival and
prolifera<on

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Func<on

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Produc<on of glucose from glycogen

For paracrine signals to act locally, secreted molecules must

not be allowed to diffuse to far

Rapidly taken up by neighboring target cells

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Types of Signaling
Endocrine signaling
•  Signaling molecules act on distant target cells
•  hormones
Paracrine signaling
•  Signaling molecules act on nearby target cells
•  neurotransmiBers, growth factors, cytokines
Autocrine signaling
•  Signaling molecules act on origina<ng cell
•  tumor growth factors
Juxtacrine signaling
•  ABached signaling molecules act on adjacent
target cells
•  integrins, cell adhesion molecules

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Molecular mechanism of signal

transduction

Six basic signaling mechanisms

1. Gated ion channels of the plasma membrane
2. Receptor enzymes, plasma membrane receptors
that are also enzymes.
3. Receptor proteins that indirectly ac<vate enzymes
like G-proteins
4. Nuclear receptors (steroid receptors) that, when
bound to their specific ligand (such as the hormone
estrogen), alter the rate at which specific genes are
transcribed and translated into cellular proteins.

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Six basic signaling mechanisms

5. Receptors that lack enzyma/c ac/vity but aBract and
ac<vate cytoplasmic enzymes that act on downstream
proteins, either by directly conver<ng them to gene-
regula<ng proteins or by ac<va<ng a cascade of enzymes
that finally ac<vates a gene regulator.

6. Receptors (adhesion receptors) that interact with

macromolecular components of the extracellular matrix
(such as collagen) and convey to the cytoskeletal system
instruc<ons on cell migra<on or adherence to the
matrix.

Signal Transduc<on Pathways

Common Elements
Signal •  Receptor mediated transfer of signal
inside of cell (mostly membrane receptors)
–  forma<on of receptor-ligand complex
–  most ligands remain outside cell
Recep<on
•  Relay and amplifica/on of signal from
Amplifica<on receptor-ligand complex
–  c a s c a d e s o f p r o t e i n a n d e n z y m e
Transduc<on
modifica<ons and product synthesis
–  GTPase switch proteins, kinases and
phosphatases, second messengers
Response(s) •  Termina/on of signal
–  hydroly<c enzymes, membrane transport