The document discusses different types of cell surface receptors involved in cell signaling. It describes ion channel-linked receptors, which allow ions to pass through the cell membrane upon ligand binding. Enzyme-linked receptors are also discussed, including receptor tyrosine kinases, tyrosine kinase-associated receptors, and receptor serine/threonine kinases. Key signaling pathways downstream of these receptors are mentioned, such as Ras-MAPK, PI3K-Akt, JAK-STAT, and TGF-beta pathways. The document provides an overview of the major receptor types and some of their associated intracellular signaling cascades involved in cell-cell communication.

1. CCELL CELL SIGNALING
[ION CHANNEL LINKED RECEPTOR
&
ENZYME LINKED RECEPTOR]
Guided by
Dr. Niraj Agarwal Sir.
Presented by
Ritima Mishra
Msc 3rd sem
Roll No. -25

2. INTRODUCTION
What is cell signaling?
All cells receive and respond to
signals from their surroundings.
Signaling molecules, which are
released by signal producing cells,
reach and transfer biological signals to
their target cells to initiate specific
cellular responses.
Stages of cell signaling
Receiving.
Transduction
Response.
What is ligand ?
 ligands are signaling
molecule.
Produced by signal producing
cell to generate response n
target cell.
Ligands may be–
cytokine hormone
steroid Growth factor.
polypeptide
What is receptor?
Receptors are Glycoprotein
on the cell surface.
Receptor helps to receive the
signals from outside and
generate responses
intracellularly.

3. Types of Receptor –
A.Intracellular receptor.
B.Cell surface receptor.
i)GPCR.
ii)Ion-Channel linked receptor.
iii)Enzyme linked receptor.

4. Signaling
Signaling molecule
Bind to receptor of
target cell.
Intracellular response by
internal molecule.
Biological effect

5. Ion Channel Linked Receptor
 Also known as cell membrane bound receptor, Ligand gated channel,
transmitter gated ion channel, ionotropic receptor.
 Here receptor is multipass protein.
 Ion channel linked receptor bind a ligand and open a channel through the
membrane that allows specific ions to pass through.
Mechanism –
 When a ligand bind with the extracellular region of the channel there is a
conformational change in the protein structure that allows ions such as
Na+,Ca+,Mg+,K+ and H+ to pass through.

6.  For example- Ligand gated channel for NTM Acetylcholine.
 NTM or peptide hormone can act as a ligand.
 As two molecules of acetylcholine binds with the receptor .
 The conformation of the receptor changed and gate is open, allows
the entry of many ions(cations specially) and small molecule.

7. ENZYME LINKED RECEPTOR
 Enzyme linked receptor are second major type of cell surface receptor.
 are single pass membrane protein.
 Having their ligand binding site outside the cell and their catalytic side inside.
 Great majority are protein kinases.(associated or itself a protein kinase).
 Kinases can phosphorylate specific protein in the target cell which again can
phosphorylate downstream proteins .
 An enzyme linked receptor also known as catalytic receptor , is a transmembrane
receptor.
 Wherer the binding of an extracellular ligand causes enzymatic activity on the
intracellular side.

8. • Receptor may have –
i)The receptor with intracellular
domain that are associated with
an enzyme.
ii)The receptor with intracellular
domain that itself act as an
enzyme.

9. There are 3 types of enzyme –linked receptor --
-
i)Receptor –Tyrosine kinase.
ii)Tyrosine-Kinase associated receptor .
iii)Receptor Serine/ Threonine kinase.

10. i) Receptor Tyrosine kinase-
 Receptor tyrosine kinases (RTK) are the high affinity cell surface receptor for
many polypeptides( growth factor , cytokinine and hormones).
 Receptor tyrosine kinase have been shown not only to be key regulator of
normal cellular processess but also have a critical role in the development and
progression of many types cancer.
 Mutation in receptor protein kinase leads to activation of receptor in absence
of ligand also and effect protein expression.
 Kinase enzymes that specifically phosphorylate the amino acid, tyrosine, termed
as tyrosine kinase.
 Ligand for RTK-
Nerve growth
factor
Platelet growth
factor
Fibroblast
Growth Factor
Hepatocyte
growth factor
Insulin growth
factor
Epidermal
growth factor

11. Structure of RTK

12. Mode of action of RTK-
 When a growth factor binds to the extracellular domain of RTK,
dimerization happen with the adjacent RTK.
 Which enables the two cytoplasmic domains to cross phosphorylate the
tyrosine residue of each other .
 This cross phosphorylation is called autophosphorylation.

13. • There are 3 major pathways can transduce a
signal from activated RTK:-
1.Ras-MAP kinase (MAPK also called as ERK-Extracellular signal
regulated kinase)
2.IP3/DAG Pathway.
3.PI-3 kinase pathway/AKT
a.mTOR
b.Insulin signaling.

14. What is a Ras?
• Belongs to GTPase family.
• Ras is monomeric g –protein(GTPase)
switch protein.
• Ras is a guanosine-nucleotide –
binding protein.
• Ras has intrinsic GTPase activity.
• Which means that protein on its own
will hydrolyze a bound GTP molecule
into GDP.
• When Ras is active,it turn on genes
involved in cell growth,differentiat-
- ion and survival.
• It anchored in the plasmamembrane.
• Mutation of it can cause cancer.
What is MAP kinase?
•MAPK-Mitogen –
activating protein kinase .
•It is a type of protein
kinase that is specific to the
amino acids serine and
threonine.

15. MODE OF ACTION :
a. Ras-MAP Kinase Pathway :-

16. Some important terms of
Ras-MAP
Kinase
Pathway:-
 SOS-Son of Sevenless.(nulcleotide
exchange factor)
GRB2-Growth Factor Binding 2
Raf-Serine/Thr kinase.(MAPKKK)
MEK-Serine/thr kinase/tyr kinase(MAPKK).
Elk-1-Transcription factor activating protein.
Fos-june-transcription factor

17. b.IP3-DAG Pathway-

18. • Some important terms of
IP3-DAG
Pathway IP3- Inositol 1,4,5 triphosphate.
PIP2-Phosphotidylinositol 4,5 –
biphosphate.
DAG-Diacylglycerol.
PKC-Protein Kinase C.

19. c.PI-3 kinase pathway/AKT-

20. • Some important terms of PI-3-Kinase
pathway
PI-3:- Phosphatidylinositol 3 Kinase.
PIP2:-Phosphatidylinositol-4,5-
biphosphate
PIP3:-Phosphatidylinositol -3,4,5-
biphosphate
PKB:-Protein Kinase B.
PDK-pkb Dependent Kinase 2

21. i) 1- mTOR pathway:-
 mTOR- Mammalian Target of Rapamycin.
 Extracellular signal require for the animal cell to grow ,divide and
survive.
 TOR- serine threonine kinase.
 Tor has two multiprotein complex-
Complex 1(mTORC1)
It has Raptor protein.
Sensitive to Rapamycin
.
mTORC1 promote protein
synthesis by phosphorylating
the eIF4E-Binding Protein by
making the Eif4e free for
translation.
Complex2 (mTORC2)
It has Rictor protein.
Insensitive to Rapamycin.
Rictor help in activation of
AKT and it regulate the
actin cytoskeleton via Rho
family GTPase.

22. • mTOR Pathway-
If extracellular growth
factor on RTK.
Activate PIP-3 Kinase.
Activate AKT/PKB
Activate mTORc1
TSC-2(GAP)
Rheb-GTP
Add phosphate at
eIF4E-BP
eEF4E active Protein synthesis

23. ii)Insulin signaling pathway-
 It’s a type of peptide hormone secreted by pancreati cells (β-langerhans
cells).
 Receptor of Insulin- Dimer (Inactive) and tetramer(active).
 Insulin receptor synthesis to maintain the blood glucose level.
 The receptor of insulin may present at liver,muscles,adipose tissue(store
glucose).
 Insulin signaling pathway – Ras dependent
Ras independent.

24. Ras dependent and Ras independent

25. ii)Tyrosine kinase associated receptor –
 Rather than processing intrinsic enzymatic activity,many enzymes linked
receptor act by stimulating intracellular protein tyrosine kinase with which
they are non-covalently associated.
 N terminal –Ligand binding domain.
 C terminal –cytosolic domain of the tyrosine kinase associated with
receptor get activated after binding with ligand.
 Enzyme cytosolic tyrosine kinase—JAK (Janus kinase).
 Maximum receptor are antigen ,peptide,(GH, prolactin),interlukins.

26. JAK-STAT Pathway

27. • Some important terms of JAK-STAT pathway-
JAK:-Janus kinase.
STAT:-Signal Transducer and Activator
of Transcription.

28. iii)Receptor Serine/Threonine kinase-
 These receptors are single pass transmembrane protein.
 There are two classes of serine/threonine kinase of receptor-TypeI
-TypeII
 Ligands are- TGF-β, BMPs ,Activins.
 This receptor donot active in homodimer form active in heterodimer form.
 Protein from this group participate in 7 metabolic pathways-
1.MAPK 2.Cytokine –cyt receptor interaction. 3.TGF-β 4.Adhrens junction.
5.Colorectal cancer. 6.pancreatic cancer. 7.Chronic myeloid leukemia.

29. Serine/ threonine kinase Pathway-

30. • Some important terms of Serine/ thr kinase
Receptor
Pathway
SMAD:-mediators of TGF-β
signal transduction.

31. Conclusion
 A signal is an entity that codes or conveys information.
 The ability of cells to perceive and correctly respond to their
microenvironment is the basis of development, tissue repair,
and immunity as well as normal tissue homeostasis.
 Errors in signaling interactions and cellular information
processing may cause diseases such as cancer, autoimmunity
and diabetes.

32. THANK YOU