Cell signaling

Signal transduction
In multicellular organisms, cells with different functions
exchange a wide variety of signals.
The signal represents information that is detected by
specific receptors and converted to a cellular response,
which always involves a chemical process. This
conversion of information into a chemical change, signal
transduction, is a universal property of living cells.
Signal transduction is the process by which a chemical
or physical signal is transmitted through a cell as a series
of molecular events, most commonly protein
phosphorylation catalyzed by protein kinases, which
ultimately results in a cellular response.
 Cell signaling
(Brief History)
In 1970, Martin Rodbell examined effects of glucagon on rat’s liver
cell membrane receptor

He revealed about guanosine triphosphate and stimulated 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 transduction
in cells”
 Signal transduction
Transduction: the action or process of converting something,
especially energy or a message, into another form

Types

Protein Phosphorylation
modification cascade

Protein conformational Protein kinases

changes are required
Production of glucose from glycogen
Example:
Tumor cells: release growth factors for their own survival and
proliferation
Function
For paracrine signals to act locally, secreted molecules must
not be allowed to diffuse to far

Rapidly taken up by neighboring target cells

 Types of Signaling
Endocrine signaling
• Signaling molecules act on distant target cells
• hormones
Paracrine signaling
• Signaling molecules act on nearby target cells
• neurotransmitters, growth factors, cytokines
Autocrine signaling
• Signaling molecules act on originating cell
• tumor growth factors
Juxtacrine signaling
• Attached signaling molecules act on adjacent
target cells
• integrins, cell adhesion molecules
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. Receptor tyrosine kinases (RTKs)…….growth factors
3. Receptor proteins that indirectly activate 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.
 Six basic signaling mechanisms
5. Receptors that lack enzymatic activity but attract and
activate cytoplasmic enzymes that act on downstream
proteins, either by directly converting them to gene-
regulating proteins or by activating a cascade of enzymes
that finally activates 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
instructions on cell migration or adherence to the
matrix. Integrins
 Signal Transduction Pathways
Common Elements
Signal • Receptor mediated transfer of signal
inside of cell (mostly membrane receptors)
– formation of receptor-ligand complex
– most ligands remain outside cell
Reception
• Relay and amplification of signal from
receptor-ligand complex
– cascades of protein and enzyme
Transduction
modifications and product synthesis
Amplification – GTPase switch proteins, kinases and
phosphatases, second messengers
Response(s) • Termination of signal
– hydrolytic enzymes, membrane transport