Protein kinases : Role in cell signaling & implication in human pathologies Jayanti Tokas 1 , Rubina Begum 1 , Shalini Jain 2 and Hariom Yadav 2 1 Department of Biotechnology, JMIT, Radaur 2 NIDDK, National Institute of Health, Bethesda,MD20892, USA Email: [email protected]
30
Embed
Protein kinases : Role in cell signaling & implication in human pathologies Jayanti Tokas 1, Rubina Begum 1, Shalini Jain 2 and Hariom Yadav 2 1 Department.
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Protein kinases : Role in cell signaling & implication in human
pathologies
Jayanti Tokas1, Rubina Begum1, Shalini Jain2 and Hariom Yadav2
1Department of Biotechnology, JMIT, Radaur
2 NIDDK, National Institute of Health, Bethesda,MD20892, USA
Kinases Protein phosphorylation cell signalingKinases Protein phosphorylation cell signaling
Reversible protein phosphorylation as a biological regulatory mechanism
Edmond H. Fischer and Edwin G. Krebs (1992 Nobel Prize for Physiology and Medicine).
Post-translational modification in the cell
• Cell growth/proliferation• Differentiation• Viability/survival• Homeostasis• Effector function (e.g. cytotoxicity, cytokine production)• Cell death
‘signal’
Signal Transduction and Kinase Pathways
Nucleus MAP kinase,• Transcription factors– Bind consensus sequence on
promoter– May form complexes– May itself be transcribed following cellular activation
Adaptor proteins
Effector enzymes
Classification
On the basis of amino acid :
Tyrosine kinases,
Serine threonine (PKC, Plk,Rho Kinases)
Receptor (EGFR,FGFR,PDGFR)
non receptor (JAK,src,Abl,MAPK)
Tyrosine kinase
structure
function:
Related pathologies
Serine threonine kinases Related pathology
Check points
Check points
Structure
Bioblar structure
N and c
N-beta sheets
C-alpha helix
ATP bind-cleft at intetrsection
How they function:
Mechanisms of Activation of Normal TKs.
survivalDifferentiation Motility Proliferation
May oligomerise
ControlAutoinhihibitory transmembrane interactions cytoplasmic juxtamembrane region further inhibits the enzyme by interacting with the kinase domain Autophosphorylation---. reorient critical amino acid residues increasing catalytic activityinhibitor proteins and lipidsIF CONTROL LOST
Loss of function
Gain of function
Mechanisms of TK Dysregulation
oPDGF EGFVEGFFGFKL
oPDGFREGFRHER2c-KITFGFR3
Overexpression of receptor or ligand
EGFRSuperfamily with 4 receptors
C-ERBB
C-ERBB2
C-ERBB3
C-ERBB4
Cell proliferationInhibition of apoptosisAngiogenesisCell motilitymetastasis