Novel vitamin K-dependent pathways regulating cell survival.
Historically, the vitamin K1-dependent proteins have been associated primarily with blood coagulation and secondarily with bone formation. Recent identification of K1-dependent proteins as specific ligands for the receptor tyrosine kinases (RTKs) that can stimulate cell replication and transformation and participate in cell survival highlighted a previously unrecognized and potentially important role for vitamin K1 in cell signaling. Growing evidence suggests that most normal and tumor cells possess an active K1-dependent gamma-carboxylation mechanism necessary for the production of gamma-carboxyglutamic acid (Gla)-containing proteins. Gla residues in proteins facilitate calcium-dependent protein/phospholipid interaction. Recent studies demonstrating the potentially positive effects of a vitamin K-dependent receptor:ligand system on cell growth and survival in general and the effects of the overexpression of these RTKs on malignant cell survival provide a new perspective on the role of vitamin K1, its dependent protein ligands, and their receptors. These cumulative observations also provide an explanation for the rigidly controlled K1 levels in the mammalian fetus and the minimal hepatic stores in the adult.
Saxena
S P
SP
Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87115, USA. ssaxena@lrri.org
Israels
E D
ED
Israels
L G
LG
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction; D014812:Vitamin K / Q000502:physiology*
D014812:Vitamin K