This signalling pathway easily to understands

1. Presented by…….
Anil
NIPER A1719PC01
Department of Pharmacology and Toxicology
TGF –β SIGNALING PATHWAY

2. CONTENTS
INTRODUCTION OF TGF
TYPES OF TGF
FUNCTIONS OF TGF-BETA
TGF-β SUPER FAMILY LIGANDS
TGF-β SIGNALING PATHWAYS

3. INTRODUCTION
TGF
TGF stands for transforming growth factor or tumour growth factor.
Polypeptide member of the transforming growth factor beta superfamily of cytokines.
It is a secreted protein that performs many cellular functions.
TGF was first identified in human platelets as a protein with a molecular mass of
25 kilodaltons with a potential role in wound healing.

4. TGF
TGF-α TGF-β
TYPES OF TGF
FUNCTION
Induce epithelial
development
Upregulate Cancer
FUNCTION
Control cell
proliferation
Immune system function
Control apoptosis

5. TGF-β
Cell proliferation
Immune regulation
Cellular differention
Tissue repair
Extra cellular
matrix production
Apoptosis
Angiogenesis
Cell growth
FUNCTION OF TGF-β

6. TGF-β Super family ligands
Nodals BMP GDF
I/II
Actin -
A
TGF-βs AMH
TGF-β Super family ligands

7. TGF-β Family
 The TGF-β family contains large number of cytokines that are both structurally and
functionally related and that act as pleiotropic regulation in a wide range of biological
processes
 It is more than 40 members of this family have been identified
 TGF-β consist three subtypes
TGF-β
TGF-
βı
TGF-
βıı
TGF-
βııı

8. TGF-β signalling pathways
SMAD dependent pathway
or
Canonical pathway
Non SMAD dependent
pathway
or
Non canonical pathway
Smad1
SMADS
R-
SMAD
Co-
SMAD
I-
SMAD
Smad 2 Smad 3 Smad 5 Smad 8 Smad 9 Smad
4
R-
SMAD
Smad 6 Smad 7

9. TGF-β
Receptor 2
Receptor recruitment
&phosphorylation
R smad &
phosphorylation
Co smad
Transcription
SMAD DEPENDENT PATHWAY

10. NON SMAD DEPENDENT PATHWAY
TGF-β
Receptor 1
phosphorylation
TRAF-6 JNK1
AKT
RAF
RAS

11. TGF-
β
Cell membrane
R1R2 R2 R1
P P
R smad
Co smad
R
smad
Co
smad
Cytoplasm
Nucleus
TAK1
JNK P38
RAS
RAF
PI3K
AKT
TRAF-
6
Smad -4
Smad-7
P
SMAD DEPENDENT & NON SMAD DEPENDENT PATHWAYS OF TGF-β
SIGNALING
Transcription of
target protein
R
smad
Co
smad
TAK1
RAS
RAF
TRAF-
6

12. Transcription
of target
protein