This document discusses receptors and their downstream signaling pathways, including JAK-STAT and MAPK pathways. It defines receptors and describes different receptor types like G protein-coupled and enzyme-linked receptors. It then focuses on the JAK-STAT pathway, identifying its components like JAK kinases and STAT transcription factors, and drugs that target this pathway for conditions like rheumatoid arthritis. Finally, it examines the MAPK pathway, identifying the MAP kinase families involved in key cellular processes and examples of drugs that inhibit parts of this pathway.

1. Presented by Shakshi Sharma
M. Pharm : Pharmacology (Ist
semester)
Department of Pharmacology
ISF college of Pharmacy, Moga

2.  Receptor
 Types of Receptor
 Enzyme linked receptor and their structure
 Cellular response
 JAK-STAT pathway
 Drugs targeted in JSAK-STAT pathway
 Physiological role of JAK-STAT pathway
 MAP kinase and their types
 Drugs targeted in MAP kinase
 Physiological role of MAP kinase signaling

3.  The concept of receptor was introduced by John
Newport Langley and Paul Ehrlich in 20th
century.
 Receptor is defined as a macromolecule or binding site
located on the surface or inside the effector cell that
serves to recognize the signal/molecule/drug and
initiate the response to it, but itself has no other
function.

4. 1. G- protein coupled receptor- e.g., Ach-
Muscarinic and Adrenergic receptors.
2. Ion channel receptor- e.g., Ach-
Nicotine, GABA, Glutamate.
3. Transmembrane enzyme linked
receptor- e.g., Insulin.
4. Receptors regulating gene expression-
e.g., Steroids, Thyroxin.

5. These are also known as Catalytic Receptor, is a
transmembrane receptor, where the binding of an
extracellular ligand causes enzymatic activity on the
intracellular side.
Example:- Insulin, Epidermal growth factor (EGF),
Nerve growth factor (NGF) receptors.

7. 7
Ligand Receptor Get
autophosphorylate
Activate ligand which
futher regulates
various pathways
PI3-K /Akt
pathway
RAS/MAPK
pathway
JAK/STAT
pathway
Binds
to

8. The JAK/STAT signaling pathway transmits
information from extracellular chemical signals to the
nucleus resulting in DNA transcription and expression
of genes involved in immunity, proliferation,
differentiation, apoptosis, and oncogenesis.

9.  JAK- Family of cytoplamic non-receptor tyrosine kinases
which get activated after the binding of a cytokine to the cell-
surface cytokine receptor.
 STAT- Family of transcription factors that become activated
when one of the tyrosine residues is phosphorylated by JAK.
 STAT3- Dimers then translocate from the cytoplasm into the
nucleus-bind to Interferon-Stimulated Response Elements.
 Cellular responses to dozens of cytokines and growth factors
are mediated by the evolutionarily conserved.

11.  TOFACITINIB – JAK-STAT inhibitor, used in
Rheumatoid arthritis.
 RUXOLITINIB – JAK inhibitor, used in
myeloproliferative disorder.
 PYRIMETHAMINE – STAT3 inhibitor, used in
chronic lymphocytic leukaemia.
 TOFACITINIB - JAK inhibitor, used in rheumatoid
arthritis.

12.  Modulates development and physiology of white
adipose tissue.
 STAT proteins regulate adipocyte differentiation.
 Adipose tissue immune cells produce JAK-STAT
activator.

13.  It is an enzyme that translocates the signals to the
nucleus and activates many transcriptional factors by
phosphorylating many different proteins that regulate
expression of important cell cycle and differentiation
specific proteins.

14.  MAP kinases are serine/threonine-specific protein
kinases that respond to extracellular stimuli
(mitogens, osmotic stress, heat shock, and pro-
inflammatory cytokines) and regulate various cellular
activities, such as gene expression, mitosis,
differentiation, proliferation, cell survival/apoptosis.
 MAP kinases are activated within the protein kinase
cascades called MAPK cascade/MAPK signaling
toolkit.

16. 1. c-Jun NH2-terminal kinases (JNKs)- this
phosphorylates Jun.
1. p38 MAPK- regulates cell death (apoptosis) and
inflammatory cytokine expression (may be important in
arthritis).
1. Extracellular signal-related kinases (ERKs)- crucial in
cell division, memory and learning (abnormal ERKs may
lead to Alzheimers).
• JNKs and p38
are also called SAPK (Stress activated
protein kinase) which gets activated on any stress. It help
the cells to survive under any condition.

17.  BRAF inhibitor:- Venurafenib, Dabarafenib
 Kinase inhibitor:- Sorafenib
 RTK inhibitor:- Gefitinib, Erlotinib

18. APOPTOSIS
INFLAMMATION
CYTOKINE
PRODUCTION
METABOLIS
M
FETAL LIVER
FORMATION