final shweta protein kinase cascade
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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
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