TY - JOUR
T1 - The Croonian Lecture 1998. Identification of a protein kinase cascade of major importance in insulin signal transduction
AU - Cohen, Philip
PY - 1999/2/28
Y1 - 1999/2/28
N2 - Diabetes affects 3% of the European population and 140 million people Worldwide, and is largely a disease of insulin resistance in which the tissues fail to respond to this hormone. This emphasizes the importance of understanding how insulin signals to the cell's interior. We have recently dissected a protein kinase cascade that is triggered by the formation of the insulin 'second messenger' Phosphatidylinositide (3,4,5) trisphosphate (PtdIns(3,4,5)P3) and which appears to mediate many of the metabolic actions of this hormone. The first enzyme in the cascade is termed 3-phosphoinositide-dependent protein kinase-1 (PDK1), because it only activates protein kinase B (PKB), the next enzyme in the pathway, in the presence of PtdIns(3,4,5)P3. PKB then inactivates glycogen synthase kinase-3 (GSK3). PDK1, PKB and GSK3 regulate many physiological events by phosphorylating a variety of intracellular proteins. In addition, PKB plays an important role in mediating protection against apoptosis by survival factors, such as insulin-like growth factor-1.
AB - Diabetes affects 3% of the European population and 140 million people Worldwide, and is largely a disease of insulin resistance in which the tissues fail to respond to this hormone. This emphasizes the importance of understanding how insulin signals to the cell's interior. We have recently dissected a protein kinase cascade that is triggered by the formation of the insulin 'second messenger' Phosphatidylinositide (3,4,5) trisphosphate (PtdIns(3,4,5)P3) and which appears to mediate many of the metabolic actions of this hormone. The first enzyme in the cascade is termed 3-phosphoinositide-dependent protein kinase-1 (PDK1), because it only activates protein kinase B (PKB), the next enzyme in the pathway, in the presence of PtdIns(3,4,5)P3. PKB then inactivates glycogen synthase kinase-3 (GSK3). PDK1, PKB and GSK3 regulate many physiological events by phosphorylating a variety of intracellular proteins. In addition, PKB plays an important role in mediating protection against apoptosis by survival factors, such as insulin-like growth factor-1.
KW - Apoptosis
KW - Diabetes
KW - IGF1
KW - Inositol phospholipid
KW - Insulin
KW - Protein kinase
UR - http://www.scopus.com/inward/record.url?scp=0033611663&partnerID=8YFLogxK
U2 - 10.1098/rstb.1999.0399
DO - 10.1098/rstb.1999.0399
M3 - Article
C2 - 10212493
AN - SCOPUS:0033611663
VL - 354
SP - 485
EP - 495
JO - Philosophical Transactions of the Royal Society B - Biological Sciences
JF - Philosophical Transactions of the Royal Society B - Biological Sciences
SN - 0962-8436
IS - 1382
ER -