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Molecular Mechanisms of Transforming Growth Factor-ß Signaling

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710

I. Introduction

II. Ligands and Receptors

A. Ligands

B. Receptors

C. Receptor kinase signaling

III. Smads

A. Cloning of the Smads

B. Smad regulation

C. Smad nuclear function

D. Smad structure

E. Smads as negative regulators

F. Smad-deficient mice

G. Smads: an emerging model

IV. TGF-ß and the Cell Cycle

A. TGF-ß induction of the CKIs

B. TGF-ß-mediated decrease in Cdc25A levels in the breast epithelial cell line MCF10A

C. TGF-ß-mediated cyclin-CDK inhibition may be common strategy to arrest cells in G₁

V. TGF-ß and Cancer

A. Receptor mutants

B. Smad mutants

C. Cell cycle mutants

D. Multilevel resistance to TGF-ß is important in multistep model of carcinogenesis

VI. Conclusions