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

Contents

• Introduction and function

• Classification

• Mechanism

• Protein kinase cascade

• Double phosphorylation

• Multi-layer perceptron

• Biological example

• References

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.

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)

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.

Protein Kinase cascade

A series of protein kinase adding a phosphate group to the next protein in the sequence.

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

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

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

Biological example

Serin/threonin kinase

Receptor based tyrosine kinase

Biological example

Non receptor tyrosine kinase

Biological example

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)

Thank you