This document provides an overview of protein kinase cascades. It begins with an introduction to protein kinases and their function in phosphorylating proteins and playing roles in cellular processes. It then discusses the classification of protein kinases based on the amino acid they phosphorylate. Next, it explains the basic mechanism of phosphorylation by protein kinases using ATP. It proceeds to describe protein kinase cascades where one kinase phosphorylates and activates the next in a chain. Examples of double phosphorylation and multi-layer perceptrons in cascades are illustrated. Finally, some biological examples of different types of protein kinases are mentioned before concluding with references.

1. Protein kinase cascade
Submitted by:
ShwetaKumari
M.Sc. Bioinformatics
4th semester
Roll no: 21
Session: 2014-16
Submitted to:
Dr. Durg Vijay Singh
Bioinformatics Programmme
Centre for Biological Science

2. Contents
• Introduction and function
• Classification
• Mechanism
• Protein kinase cascade
• Double phosphorylation
• Multi-layer perceptron
• Biological example
• References

3. Introduction & Function
• An enzyme that catalyze phosphorylation (use
ATP to phosphorylate proteins)
• Attaches a phosphate (PO₄) group to a
protein for their activation.
• Play crucial roles in major cellular processes
• signal transduction,
• cell differentiation,
• cell proliferation and
• cell cycle progression.

4. Classification
On the basis of amino acid:
1. Tyrosine kinases
a. Receptor (EGFR, FGFR, PDGFR)
b. non receptor (JAK, src, Abl, MAPK)
2. Serine threonine (PKC, Plk, Rho Kinases)

5. Mechanism
ATP binds to the active site of the kinase.
Binding of the substrate to the active site.
Phosphorylation (γ-phosphate of ATP is
transferred to a Ser, Thr or Tyr residue of the
substrate/protein)
Substrate is released from the kinase.
Release of ADP from the active site. The basic catalytic cycle for substrate
phosphorylation by a kinase.

6. Protein Kinase cascade
A series of protein kinase adding a
phosphate group to the next protein
in the sequence.

7. Fig. Protein kinase cascade: Ligand binds
the receptor which leads, usually through
adaptor proteins, to phosphorylation of
kinase X. Kinase X is active when
phosphorylated, X-p. X-p phosphorylates
kinase Y. Y-p, in turn,phosphorylates Z.
The last kinase, Z-p, phosphorylates
transcription factor T, making it active, T*.
T* enters the nucleus and activates (or
represses) transcription of genes.
Phosphatases remove the phosphoryl
groups (light arrows).
Protein Kinase cascade

8. Fig. Double phosphorylation
in protein kinase cascades:
Protein kinases X,Y and Z are
usually phosphorylated on
two sites, and often require
both phosphorylations for full
activity.
Double phosphorylation

9. Fig. Multi-layer
perceptrons in protein
kinase cascades.
Several different
receptors in the same
cell can activate
specific top-layer
kinases in response to
their ligands. Each
layer in the cascade
often has multiple
kinases, each of which
can phosphorylate
many of the kinases in
the next layer.
Multi-layer perceptrons

10. Biological example
Serin/threonin kinase

11. Receptor based tyrosine kinase
Biological example

12. Non receptor tyrosine kinase
Biological example

13. References
Text Book
 Uri Alon, An Introduction to Systems Biology: Design Principles of Biological
Circuits, 2/e, CRC Press, (2006).
 Literature References
 S.S. Taylor, J. Yang, J. Wu, N.M. Haste, E. Radzio-Andzelm, G. Anand. PKA:
a portrait of protein kinase dynamics. Biochimica et Biophysica Acta 1697
(2004) 259– 269.
 Jane A. Endicott, Martin E.M. Noble and Louise N. Johnson. The Structural
Basis for Control of Eukaryotic Protein Kinases.Annu. Rev. Biochem. 2012.
81:587–613
 Shchemelinin, Sefc, E. Nečas. Protein Kinases, Their Function and Implication
in Cancer and Other Diseases. Folia Biologica (Praha) 52, 81-101 (2006)

14. Thank you