Abstract

An historical account of how the term “signal transduction” entered biomedical research and how
stimulus-response coupling, hormones, neurotransmitters, growth factors, and their receptors were
brought to light. It pays tribute to the wisdom of our forebears, whose freedom of thought and
sometimes serendipitous discoveries in the nineteenth and early twentieth centuries led to the creation
of the modern sciences. Introduction to signal transduction provides an overview of the many
mechanisms that cells employ to create a symbolic representation of their environment. It deals with
first messengers (ligands) and receptors and how they interact, their basic pharmacology, and their
modes of signal transmission into the cell. It deals with transducers, effectors, and second messengers.
It provides an overview of allosteric regulation and posttranslational mechanisms including
methylation, acetylation, glycosylation, ubiquitinylation, sumoylation, and phosphorylation.

Terms to know/Keywords.

 Receptors and their ligands

 Receptor tyrosine kinases.
 Five types of receptors Signaling mechanisms
 Tyrosine phosphatases.
 Protein kinases catalyze the phosphate transfer
 Phosphorylation
 Signal termination

Learning outcome.

 Define signal transduction.

 Describe the types of receptors and molecular composition
 Describe the basic principles of signal transduction
 Explain pathways of insulin signal transduction with illustration.

1) Signal transduction
The expression signal transduction first made its mark in the biological literature around 1974
and as a title word in 1979.Signal transduction or transmembrane signaling is a mechanism
where cell communicate with the extracellular environment and respond temporally to
external cues. Receptor mediated transduction is a fundamental cellular signal
transduction which is essential for the communication events at the cell
surface for interaction with extracellular environment. There are four general
cases of signal transducing receptors
 2) Types of receptors and molecular composition

1.There are five main types of enzyme-linked receptors:

 Tyrosine Kinase : Contains intrinsic tyrosine kinase activity
 Serine/Threonine Kinase: Contains intrinsic serine/threonine kinase activity
 Guanylyl Cyclases: Contain intrinsic cyclase activity
 Tyrosine-Kinase Associated Receptors: Receptors that associate with proteins that
have
 Tyrosine kinase activity (Cytokine Receptors)
 Tyrosine Phosphatases
2. Receptors that are coupled, inside the cell, to G proteins (7-TM Receptors)
 7-TM receptors are activated by a wide variety of ligands including light, olfactory
stimulants, peptides, hormones and neurotransmitters.
 They are grouped into 6 classes based on sequence homology and functional
similarity:
• Class A -Rhodopsin-like
• Class B -Secretin receptor family
• Class C -Metabotropic glutamate/pheromone
• Class D -Fungal mating pheromone receptors
• Class E -Cyclic AMP receptors
• Class F -Frizzled/Smoothened
3. Receptors that are found intracellular and upon ligand binding directly alter gene
transcription (Nuclear Receptors)
4. Ligand-gated ion channels.
 3) Describe the basic principles of signal transduction

There are three stages in the process of cell signaling or communication:

1. Reception-a protein at the cell surface detects chemical signals.

2. Transduction-a change in protein stimulates other changes including signal-transduction

pathways.

3. Response-almost any cellular activity.

Once the target cell receives the signal molecule it converts the signal to a form that can bring
about a specific cellular response. This often occurs in a series of steps called a signal
transduction pathway. Signal molecules bind to receptor protein, in cell membranes, and
generally cause a conformational change in the proteins. This change in conformation is
transmitted to the cytoplasmic domain or part of the receptor molecule. The transformed
molecule interacts with the information-relaying molecules in the cytoplasm. These
molecules are small molecules present in the cytoplasm known as secondary messengers.
Calcium ions and Cyclic AMP (cAMP) are examples. This further starts a series of chain
reactions, which ultimately reaches the target gene and causes its expression or repression. A
single cell may have several types of receptors each binding to a specific signal molecule. A
cell can receive a number of different types of signal molecules simultaneously. Once the
signals are relayed into the cells, they are selectively routed through various signal pathways
to the target, which may be a gene or a protein. Usually the cellular response for a signal
molecule may be a change in gene expression, change in ion permeability, or a change in the
enzyme activity or protein three-dimensional structure, which ultimately affects the
metabolism of the cell or organism.
 4) Explain pathways of insulin signal transduction with illustration.

Insulin is an anabolic peptide hormone secreted by the b-cells of the pancreas that plays a
critical role in the regulation of human metabolism. Insulin is the main hormone that
regulates critical functions of energy including glucose and lipid metabolism.Insulin
stimulates the insulin receptor tyrosine kinase (IR), which phosphorylated and recruited
various substrate adapters such as the protein family IRS. Afterwards, tyrosine
phosphorylated IRS displays binding sites for numerous signals partners. PI3 K plays a major
role in insulin f, among others

Activated Akt induces glycogen synthesis through GSK-3 inhibition; protein synthesis
through mTOR and downstream elements; and cell survival through multiple pro-apoptotic
agents inhibition (Bad, FoxO transcription factors, GSK-3, and MST1). Akt phosphorylates
and inhibits FoxO transcription factors directly, which control metabolism and autophagy,
too. Inversely, it is known that AMPK regulates FoxO3 directly and activates the
transcription activity. Insulin signaling also has growth and mitogenic effects, which are
mostly mediated by the Akt cascade and the Ras / MAPK pathway activation.

The insulin signaling pathway inhibits autophagy via the Akt and mTORC1-inhibited ULK1
kinase, and activated by AMPK. Insulin stimulates the absorption of glucose into the muscle
and adipocytes by translocating GLUT4 vesicles to the plasma membrane. GLUT4
translocation includes CAP's PI3K / Act pathway and IR-mediated phosphorylation, and
CAP: CBL: CRKII complex creation.

Additionally, insulin signaling inhibits gluconeogenesis in the liver by disrupting binding to

CREB / CBP / mTORC2. Insulin signaling induces synthesis of fatty acid and cholesterol by
regulating transcription factors in SREBP. The insulin signaling also promotes the synthesis
of fatty acids by activating USF1 and LXR. A negative feedback signal from Akt / PKB,
PKC alle, p70 S6 K, and MAPK cascades results in serine phosphorylation and IRS signaling
inactivation.
 References
 Phases of Signal Transduction - Cell Signaling Tutorial. (n.d.). Retrieved from
https://sites.google.com/site/cellsignalingtutorialphsapbio/phases-of-signal-
transduction.
 Gomperts, B. D. (n.d.). Signal Transduction. Retrieved from
https://books.google.com.my/books?
id=pJ4tXpczp6QC&printsec=frontcover&dq=definition+signal+transduction&hl=en
&sa=X&ved=0ahUKEwjGysK62_7mAhX-
zTgGHSv9AhQQ6AEIKTAA#v=onepage&q=definition signal transduction&f=false.
 Ahmed, Firoz & Ansari (2013). A Molecular Bridge: Connecting Type 2 Diabetes and
Alzheimer's Disease.. CNS & neurological disorders drug targets. 13.