Tirosin Kinase Receptor (RTK)

DEFINITION

A tyrosine kinase is an enzyme that ON

can transfer a phosphate group CELLULAR FUNCTION
from ATP to the tyrosine residues of OFF
specific proteins inside a cell.

Receptor tyrosine kinases (RTKs) are

enzyme-linked receptors localized at
the plasma membrane containing an
extracellular ligand-binding domain, a
transmembrane domain, and an
intracellular protein–tyrosine kinase
domain.
Receptor tyrosine kinases (RTKs) are a
subclass of tyrosine kinases that are
involved in mediating cell-to-cell
communication and controlling cell
growth, motility, differentiation, and
metabolism. There are 58 known RTKs in
humans with 20 families.
 EGFR/ErbB1

CLASSIFICATION
ErbB2

EGFR ( Epithelial GF)

ErbB3
VEGFR ( Vascular Growth Factor Receptor
endothelial GF)
ErbB4.
• GF receptors are RTKs that are responsible for the growth of various
TrkA partsof the cell

Insulin Receptor
NGF/Tropomyosin receptor
R.Growth TrkB
kinases ( Nerve GF) • The insulin receptor is a dimeric receptor consisting of 2 subunits a & B
Factor
linked by disulfide bonds. The a chain is extracellular and is the insulin
PDGFR
TrkC
RTK R.Sitokin (platelet derived GF) binding domain, while the B chain is membrane-bound. The binding of a

M-CSF ( Macrophage ligand (insulin) to the a subunit of the receptor will cause the B subunit

R. Insulin colony GF) to undergo autophosphorylation which in turn triggers its catalytic
activity. One of the main effectors for insulin receptors is insulin
FGFR ( fibroblast GF)
receptorsubstrate 1 (IRS-1).

insulin-like growth
factor—1 (IGF-1)

Ikawati, Z. (2018).
CLASSIFICATION

ICyctokine Receptor

• Cytokines are endogenous protein compounds released by cells to communicate

with each other (cross-talk). This protein has a low BM (10.30 kDa) and mediates
various functions related to the immune system and various organs in the body,
such as cell proliferation and differentiation, fibrosis, hematopoiesis, inflammation
and repair of the injured body.
CLASSIFICATION 2. INHIBITOR RTK
Table 1. List of FDA-approved small molecule protein kinase
1. PATHWAYS inhibitors (updated by 18 August 2019).
RAS/MAPK pathway is a central
regulator of metabolism, cell cycle, cell
proliferation, dierentiation, and
migration, for example receptor growth
factor such as plateled-derived growth
factor (PDGF), the epidermal growth
factor (EGF), the fibroblast growth
factor (FGF) and insulin receptor.

JAK/STAT pathways which is activated by

cytokines and controlling synthesis and
releasing inflammation mediatory.

Two type-C inhibitors, namely rosmarinic acid (RA) and EGCG

MECHANISM OF ACTIVATION AND INHIBITION

Figure 1: RTK activation involves the joining together and phosphorylation of proteins.
On the left, an unactivated RTK receptor (pink) encounters a ligand (red). Upon binding,
the receptor forms a complex of proteins that phosphorylate each other. In turn, this
phosphorylation affects other proteins in the cell that change gene transcription (not
shown).
© 2010 Nature Education All rights reserved.
INSULIN RECEPTOR
Insulin is a polypeptide hormone
that is secreted from beta cells of
the pancreas which regulating
glucose uptake and utilization in
cells. Insulin is also known as an
anabolic hormone and is involved
in the synthesis of glycogen,
proteins and lipids.

A defect in insulin secretion or

action leads to aberrant glucose
homeostasis and diabetes.

The insulin receptor (IR) is

composed of two extracellular –α-
subunits and two transmembrane
β-subunits linked to each other by
disulfide bonds

Figure 2. Insulin Signalling Pathway

REFERENCES
• Du, Z. & Lovly, CM. 2018. Review Mechanisms of receptor tyrosine kinase activation in cancer.
Molecular Cancer. 17, 58.
• Trenker, Raphael & Natalia Jura. 2012. Reseptor Tyrosin Kinase activation: from the ligand
perspective. Curr Opin Cell Biol.
• Pottier, C., et al. 2020. Tyrosine Kinase Inhibitors in Cancer: Breakthrough and Challenges of
Targeted Therapy. Cancers. 12, 731.
• Cheng Hsu, K. 2015. Anchor-based classification and type-C inhibitors for tyrosine kinases. Nature.
• Srivastava, A.K., Bajpai, P., Jain, A. Insulin Action. Post-Receptor Mechanisms. Elsevier Inc.