Signal transduction modules Signalling pathways control cell functions Signal transduction modules

Signal transduction modules Signalling pathways control cell functions Signal transduction modules www.phwiki.com

Signal transduction modules Signalling pathways control cell functions Signal transduction modules

Prouty, Raymond, Contributing Editor has reference to this Academic Journal, PHwiki organized this Journal What can we learn from the identification of specific molecular abnormalities in malignant disease Insights into normal cell biology Targets as long as diagnosis in addition to follow-up Targets as long as rational drug design Conventional cytotoxic drugs mainly act by causing DNA damage in addition to cell death Studying the biology of cancer cells may provide new targets as long as drug development Signal transduction modules Molecular links between changes in cell environment in addition to cellular responses

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Signalling pathways control cell functions Replicate Live/Die Move Signal transduction modules Molecular links between changes in cell environment in addition to cellular responses e.g. Erythropoietin in addition to prevention of apoptosis in erythroid progenitors G-CSF in addition to proliferation in myeloid progenitors (Hanahan & Weinberg (2000) Cell 100, 57) The hallmarks of cancer Many of these features may result from abnormalities in signalling components

Lig in addition to binding dimerizes receptor tyrosine kinases resulting in their activation No lig in addition to Monomeric receptor Lig in addition to present Dimeric receptor A number of signalling modules link growth factor receptor binding to changes in cell function Activation of gene transcription Ras PI3-kinase STAT MAPK PKB Ras.GDP Ras.GTP ON OFF GTPase activating protein e.g. NF-1 Proliferation Survival Movement Exchange factor e.g. SOS The Ras protein acts as a molecular switch in response to changes in the external environment of the cell Growth factor

Recruitment of a Grb2-SOS complex to an activated receptor tyrosine kinase mediates Ras activation RAS GDP GTP Examples of signalling pathway abnormalities in haematological malignancy Aberrant tyrosine kinase Bcr-Abl CML activity Increased Ras activity point mutation AML loss of NF1

The constitutive activity of the Bcr-Abl tyrosine kinase bypasses the requirement as long as growth factors Bcr-Abl Activation of gene transcription Increased proliferation/survival Ras PI3-kinase STAT MAPK PKB Examples of signalling pathway abnormalities in haematological malignancy Aberrant tyrosine kinase Bcr-Abl CML activity Increased Ras activity point mutation AML loss of NF1

AML AML Normal Ras proteins are frequently activated by point mutation in human cancers Ras.GDP MUTANT Ras.GTP ON OFF NF-1 Proliferation Survival Invasion Exchange factor e.g. SOS Carcinoma pancreas colon thyroid AML Myeloma Loss of the NF-1 protein results in excessive Ras activation Ras.GDP Ras.GTP ON OFF Proliferation Survival Invasion Neurofibromatosis Myeloid leukaemias

Molecular targets in leukaemia therapy Signal transduction pathways Dysregulated kinases eg Bcr-Abl Mutant Ras proteins Apoptosis pathways Bcl-2, NF-kappaB, p53 Differentiation pathways Retinoic acid receptor Histone deacetylases Imatinib mesylate inhibits the activity of Bcr-Abl by competing with ATP in addition to is effective in the treatment of CML Addition of a farnesyl (C15) moiety is required as long as Ras proteins to be active Ras inactive -CAAX Ras -C-OMe F active Cytoplasm Plasma membrane Farnesyl transferase

Targeting Ras proteins by inhibiting membrane localisation Ras inactive -CAAX Cytoplasm Plasma membrane Farnesyl transferase FT Inhibitors The transcription factor NF-kB induces transcription of pro-survival genes in addition to is constitutively activated in a variety of tumours IkB NF-kB IKK1 IKK2 NEMO NF-kB Increased transcription eg Bcl-2 NIK Degradation by proteasome P Inhibitors of proteasomal activity prevent NF-kB activation by blocking IkB degradation IkB NF-kB IKK1 IKK2 NEMO NIK P Proteasome inhibitor Eg PS-341 Reduced transcription IKK inhibitors

Prouty, Raymond Vertiflite Contributing Editor www.phwiki.com

What can we learn from the identification of specific molecular abnormalities in malignant disease Insights into normal cell biology Targets as long as diagnosis in addition to follow-up Targets as long as rational drug design

Prouty, Raymond Contributing Editor

Prouty, Raymond is from United States and they belong to Vertiflite and they are from  Westlake Village, United States got related to this Particular Journal. and Prouty, Raymond deal with the subjects like Engineering

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