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Endocrine Reviews 23 (6): 787-823
Copyright © 2002 by The Endocrine Society

Genetic Analysis of the Mammalian Transforming Growth Factor-ß Superfamily

Hua Chang, Chester W. Brown and Martin M. Matzuk

Departments of Pathology (H.C., M.M.M.), Molecular and Human Genetics (C.W.B., M.M.M.), Molecular and Cellular Biology (M.M.M.), and Pediatrics (C.W.B.), and Program in Developmental Biology (H.C., M.M.M.), Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030

Correspondence: Address all correspondence and requests for reprints to: Martin M. Matzuk, M.D., Ph.D., The Stuart A. Wallace Chair and Professor, Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030. E-mail: mmatzuk{at}bcm.tmc.edu

Members of the TGF-ß superfamily, which includes TGF-ßs, growth differentiation factors, bone morphogenetic proteins, activins, inhibins, and glial cell line-derived neurotrophic factor, are synthesized as prepropeptide precursors and then processed and secreted as homodimers or heterodimers. Most ligands of the family signal through transmembrane serine/threonine kinase receptors and SMAD proteins to regulate cellular functions. Many studies have reported the characterization of knockout and knock-in transgenic mice as well as humans or other mammals with naturally occurring genetic mutations in superfamily members or their regulatory proteins. These investigations have revealed that TGF-ß superfamily ligands, receptors, SMADs, and upstream and downstream regulators function in diverse developmental and physiological pathways. This review attempts to collate and integrate the extensive body of in vivo mammalian studies produced over the last decade.




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