Life started with unicellular forms having a limited number of genes and proteins.

As a result,

Cell signalling was less complex. With the evolution of multi-cellular life forms, the number of
genes

has increased, new signalling intermediates have been added, and the signalling networks have
become

more complicated. This addition of a novel array of signaling proteins contributes to diverse
responses
to the same stimuli across different phyla. Complex domain architecture of proteins in animals
when compared to plants and lower organisms enables the ramification of the signal transduction
process through different proteins. Genome studies in Protists have revealed a great variety in the
genome in terms of regulatory proteins it encodes for, implying the role of signaling protein in
determining diversity in eukaryotes.

Cells receive and respond to extracellular cues through receptors. The first response is triggering

complex signaling networks that relay extracellular cues into the cell, culminating in the
reprogramming

of various biochemical, genetic, and structural processes. The cellular signaling starts as soon as
the

first messenger (the ligand) binds to its receptor—a protein with the complementary structure on
a
transmembrane protein or within the cell. The binding of the ligand induces conformational
changes
to the receptor and activates well-controlled sets of reactions carried out by the second messengers
or signaling intermediates that transduce the message from the receptor to the quantifiable effector
functions. Thus, cell signaling is a crucial cog in the cellular response system. The discovery of

cellular signaling dates back to 1855 when Claude Bernard described how certain ‘internal
secretions’
of ductless glands, released into the bloodstream, can have effects on distant cells. Around 1880,
British naturalist Charles Darwin and his son Francis Darwin discovered a similar phenomenon of
phototropism of coleoptile (shoot tips) in plants and inferred “Some influence is transmitted from
the tip to the more basal regions of the shoot thereby regulating growth and inducing curvature”.

This transmittable factor or messenger was later termed as auxin. A few years later, John Langley
and

his student Thomas Elliott discovered a ‘receptive substance’ or receptors while studying
sympathetic

neuro-effector transmission . Later in 1905, Ernest Starling first coined the word ‘hormone’ (Gr.,
arousing or excite) to explain, “The chemical messengers which spread from cell to cell along the
bloodstream, may coordinate the activities and growth of different parts of the body” . Following

the discoveries of the messengers and receptors, the downstream intracellular events started
unfolding
during the 1950s. Rita Levi-Montalcini discovered that tumor extracts can cause neurite outgrowth
and identified the factor as the nerve growth factor (NGF) . The discovery of inositol phosphate
pathway [5], phosphorylation-dependent proteins , and the finding that skeletal contraction occurs

on injecting Ca2+ into the cells and that binding of adrenaline and glucagon to cellular receptors
leads
to the generation of cyclic adenosine monophosphate (cAMP) , further unraveled the details of
cellular signaling. This was followed by the discovery of epidermal growth , G-proteins , tumor
necrosis factor , and of a retroviral Src protein that functions as a tyrosine-specific kinase .
All these discoveries led to an enhanced understanding of how cells receive, perceive, and decode
the signal.

References

Darwin, C. The power of movement in plants; D. Appleton and Company: New York, NY,
USA, 1897.