the way of communication cell to cell or cell to their environment. they produce some stimuli to correspond to surroundings for survival. Cell signalling helps to defend, survive, production of chemicals and lots of other things. signalling can external and internal. in this presentation, paths are elaborated externally and internally. Hope it will help to understand cell signal in better way.

2. Cell Signaling
Presented By: Aneela Rafiq,
Biotechnology

3. General principle of cell
communication
• Prokaryotes and eukaryotes both communicate through
signals.
• Budding yeast: it secretes a peptide mating factor
that signals cells of the opposite mating type to stop
proliferating and prepare to mate. diploid cell which
generating haploid cells with new assortments of
genes

4. A) cells are normally spherical).B) in response to
mating factor they put out a protrusion towards
the source of mating

5. Extracellular Signal Molecules Bind to
Specific Receptors
• These include proteins, small peptides, amino
acids, nucleotides, steroids, retinoid, fatty acid
derivatives, and even dissolved gases such as
nitric oxide and carbon monoxide.
• Diffusion,exocytosis,displaying on extracellular
membrane
• Target cells respond by mean of proteins on their
surface the “receptor”

7. Extracellular Signal Molecules Can Act Over
Either Short or Long Distances
• Contact dependent signaling
• paracrine signaling: for short distance other wise it would
be destroyed by neighboring target cells .
• Synaptic cleft: between neurons of specialized organisms
for far away target by axons nerve impulse is send that
releases the neurotransmitters
• Endocrine cell :that control the behavior of a cell
here signaling molecules releases the hormones in blood
stream, is relatively slow and is diluted

9. Autocrine Signaling Can Coordinate Decisions by
Groups of Identical Cells
• Development decision signals to cell of same
type .
• used to encourage groups of identical cells to
make the same developmental decisions.
• during which a group of identical cells can
respond to a differentiation-inducing signal but
a single isolated cell of the same type cannot.
• cancer cells often use autocrine signaling

10. A group of identical cells produces a higher concentration
of a secreted signal than does a single cell. When this signal
binds back to a receptor on the same cell type, it
encourages the cells to respond coordinately as a group

11. Gap Junctions
• Gap Junctions Allow Signaling Information to Be Shared by
Neighboring Cells
• specialized cell-cell junctions
• Ca2 + and cyclic AMP
• electrically, with intracellular electrodes, or visually, after the
microinjection of small water-soluble dyes

12. Each Cell Is Programmed to Respond to Specific
Combinations of Extracellular Signal Molecules
• Typical cell expose to different signals
• signals can be soluble, bound to the extracellular matrix, or bound
to the surface of a neighboring cell
• deprived of these signals apoptosis

13. Different Cells Can Respond Differently to
the Same Extracellular Signal Molecule
• varies according to the set of receptor proteins the cell possesses
• varies according to the intracellular machinery by which the cell
integrates and interprets the signals it receives
• , a single signal molecule often has different effects on different
target cells.
• Example: neurotransmitter acetylcholine
stimulates the contraction of skeletal muscle cells
decreases the rate and force of contraction in heart muscle cells

14. Nitric Oxide Gas Signals by Binding Directly to
an Enzyme Inside the Target Cell
• Extracellular signals hydrophilic molecules binds to the receptor
Hydrophobic plasma membrane
• Example :
 Regulate smooth muscle contraction
Acetylcholine autonomic nerves walls of blood vessels cause
relaxation of smooth muscles indirectly act on the endothelial cell
release of NO mechanism of action of nitroglycerine angina
nitroglycerine converted into no relaxation
• Example in animals
Carbon monoxide (CO) stimulating guanylyl cyclase across the
target-cell plasma membrane regulate gene transcription

16. • Nuclear Receptors As Ligand-activated Gene Regulatory Proteins
• The Three Largest Classes of Cell Surface Receptor Proteins
• Most Activated Cell Surface Receptors spread Signals Through Small
Molecules and a Network of Intracellular Signaling Proteins

17. Nuclear Receptors As Ligand-activated Gene
Regulatory Proteins:
• Diffusion and binding to intracellular receptor proteins by
hydrophobic signal molecules.
• Binding to receptor proteins Activation bind to DNA
regulate transcription.
• Receptors are structurally related

18. The hormones functioning as signaling
molecules:
• Steroid hormones, made of cholesterol.
• Cortisol, in the cortex of the adrenal glands, effects metabolism.
• steroid sex hormones.
• Vitamin D, regulates Ca2+ metabolism, Ca2+ uptake in gut, reduce
excretion in kidneys.
• Thyroid hormones, amino acid tyrosine, ˂ metabolic rate.
• These signal molecules are insoluble in water

19. The intracellular receptors for different
hormones:
• Receptors bind to DNA sequences adjacent to genes of ligands.
• Transcriptional response;
• Activation of a small number of specific genes primary
response, protein activate other genes secondary response.

20. The Three Largest Classes of Cell Surface Receptor
Proteins:
• Water-soluble signal molecules bind to receptor proteins on surface of
target cells.
Ion channel linked receptors: e.g; active transport

21. 2. G protein linked receptors:

22. 3. Enzyme linked receptors:

23. Most Activated Cell Surface Receptors spread
Signals Through Small Molecules and a
Network of Intracellular Signaling Proteins:
• Signals received, spread into cell interior by small and large Intracellular
signaling molecules.
• Small intracellular signaling molecules, second messengers.
• Cyclic AMP and Ca2+, water-soluble, diffuse in the cytosol.
• Diacylglycerol, lipid-soluble, diffuse in the plane of the cell membrane
• large intracellular signaling molecules
• Activate next signaling protein in chain or produce small intracellular
mediators.

24. Classification of large intracellular signaling
molecules:
• Relay proteins
• Messenger proteins
• Adaptor proteins
• Amplifier proteins
• Transducer proteins
• Bifurcation proteins
• Integrator proteins

25. Other types of intracellular proteins:
• Anchoring proteins
• Scaffold proteins

26. Some Intracellular Signaling Proteins Act as
Molecular Switches
• Molecular switches
• Another process switch off
• Switching off is very important
• Two classes

27. Classes of molecular switches
1. Phosphorylation
2. GTP-binding protein

28. Phosphorylation
• Gain/lose phosphate group
• Largest class; phosphorylation
• Protein kinase/protein phosphatase
• Phosphorylation cascade
• Types of protein kinase
• Distinct types of protein kinase

29. GTP-binding protein
• Hydrolyze; GTP into GDP
• Types of GTP-binding protein
• Vesicular traffic
• Others processes

30. Molecular switches

31. Intracellular Signaling Complexes Enhance the
Speed, Efficiency, and Specificity of the Response
• G-protein-linked or enzyme-linked receptor
• Activates multiple parallel signaling pathways
• Influence multiple aspects

32. Two cases that the cell uses to achieve specificity
1. Scaffold proteins
2. Assembly of proteins

33. Scaffold proteins
• Signaling complex
• Unwanted cross talk
• Freely diffusible

34. Assembly of proteins
• Assemble around receptor
• Cytoplasmic tail
• Phosphorylated amino acids serve as docking sites
• Modified phospholipid molecules

35. Two types of intracellular signaling complexes

36. Interactions Between Intracellular Signaling Proteins Are
Mediated by Modular Binding Domains
• Binding domains
• Particular structural motif
• Multiple combinations, like Lego bricks
• New signaling pathways
• Src homology 2 (SH2) domains and phosphotyrosine-binding (PTB)
domains

37. A hypothetical signaling pathway using modular
binding domains

38. Cells Can Respond Abruptly to a Gradually
Increasing Concentration of an Extracellular Signal
• Many responses to extracellular signal molecules, however, begin
more shortly as the concentration of the molecule increases. (Ghosh
& Greenberg, 1995).
• Steroid hormone-induced responses (Ghosh & Greenberg, 1995).
• All-or-none threshold responses (Ghosh & Greenberg, 1995).

39. A Cell Can Remember the Effect of Some
Signals
• After the signal has disappeared, the effect of an extracellular signal
on a target cell can, in some cases, continue well. For example
(Gotthardt et al., 2000)
• Autophosphorylation (Gotthardt et al., 2000)
• Turn on a series of muscle-specific gene regulatory proteins (Gotthardt
et al., 2000)

40. Cells Can Adjust Their Sensitivity to a Signal
• In responding to many types of stimuli, cells and organisms are
able to detect the same percentage of change in a signal over a
very wide range of stimulus intensities (Ahmad & Xiang, 2011).

41. Conclusion
• Each cell respond to a specific set of extracellular signals produced by
other cells.
• These signals act in various combinations to regulate the behavior of the
cell.
• Ion-channel-linked receptors.
• G-protein.
• Enzyme-linked receptors
• Cell can respond abruptly to a gradually increasing concentration of an
extracellular signal
• A Cell Can Remember the Effect of Some Signals
• Cells Can Adjust Their Sensitivity to a Signal

42. References
• Ahmed, K. A., & Xiang, J. (2011). Mechanisms of cellular communication
through intercellular protein transfer. Journal of cellular and molecular
medicine, 15(7), 1458-1473.
• Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P.
(2002). Molecular biology of the cell, (4th ed.). New York: Garland
Science.
• Ghosh, A., & Greenberg, M. E. (1995). Calcium signaling in neurons:
molecular mechanisms andcellular consequences. Science, 268(5208),
239.
• Gotthardt, M., Trommsdorff, M., Nevitt, M. F., Shelton, J., Richardson, J.
A., Stockinger, W., ... & Herz, J. (2000). Interactions of the low density
lipoprotein receptor gene family with cytosolic
• adaptor and scaffold proteins suggest diverse biological functions in
cellular communication and signal transduction. Journal of Biological
Chemistry, 275(33), 25616-25624

43. • .Lee, T. H., D’Asti, E., Magnus, N., Al-Nedawi, K., Meehan, B., & Rak, J.
(2011). Microvesicles
• as mediators of intercellular communication in cancer, the emerging
science of cellular ‘debris’.
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• Mayer, M. P., & Bukau, B. (2005). Hsp70 chaperones: cellular functions
and molecular
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• Preissner, K. T., Kanse, S. M., & May, A. E. (2000). Urokinase receptor: a
molecular organizer in
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