Current ideas on the biology of IGFBP-6: More than an IGF-II inhibitor?
IGFBP-6 binds IGF-II with higher affinity than IGF-I and it is a relatively specific inhibitor of IGF-II actions. More recently, IGFBP-6 has also been reported to have IGF-independent effects on cell proliferation, survival, differentiation and migration. IGFBP-6 binds to several ligands in the extracellular space, cytoplasm and nucleus. These interactions, together with activation of distinct intracellular signaling pathways, may contribute to its IGF-independent actions; for example, IGF-independent migration induced by IGFBP-6 involves interaction with prohibitin-2 and activation of MAP kinase pathways. A major challenge for the future is delineating the relative roles of the IGF-dependent and -independent actions of IGFBP-6, which may lead to the development of therapeutic approaches for diseases including cancer.
Department of Medicine (Alfred), Monash University, Prahran 3181, Australia; Department of Endocrinology and Diabetes, Alfred Hospital, Melbourne 3004, Australia. Electronic address: leon.bach@monash.edu.
Leon A
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Bach
D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000378:metabolism / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000091402:Prohibitins; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction
D018976:Insulin-Like Growth Factor Binding Protein 6; D000091402:Prohibitins; D012097:Repressor Proteins; D007335:Insulin-Like Growth Factor II; D020928:Mitogen-Activated Protein Kinases
Differentiation; Insulin like growth factor; Insulin like growth factor binding protein-6; Migration; Proliferation; Survival