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Specificity, diversity, and regulation in TGF‐β superfamily signaling
Author(s) -
PIEK ESTER,
HELDIN CARLHENRIK,
DIJKE PETER TEN
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.15.2105
Subject(s) - smad , r smad , microbiology and biotechnology , biology , receptor , signal transduction , transcription factor , growth differentiation factor , acvrl1 , transforming growth factor , bmpr2 , superfamily , bone morphogenetic protein , genetics , gene , tgf alpha , endoglin , growth factor , stem cell , cd34
Transforming growth factor‐β (TGF‐β) superfamily members are multifunctional cell‐cell signaling proteins that play pivotal roles in tissue homeostasis and development of multicellular animals. They mediate their pleiotropic effects from membrane to nucleus through distinct combinations of type I and type II serine/threonine kinase receptors and their downstream effectors, known as Smad proteins. Certain Smads, termed receptor‐regulated Smads, become phosphorylated by activated type I receptors and form heteromeric complexes with a common‐partner Smad4, which translocates into the nucleus to control gene transcription. In addition to these signal transducing Smads, inhibitory Smads have been identified that inhibit the activation of receptor‐regulated Smads. In contrast to the still growing TGF‐β superfamily (with ~30 members in mammals), relatively few type I and type II receptors as well as Smads have been identified. We will focus on recent insights into the molecular mechanisms by which signaling specificity between different TGF‐β superfamily members is achieved and regulated, and how a single family member can elicit a broad scala of biological responses.—Piek, E., Heldin, C.‐H., ten Dijke, P. Specificity, diversity, and regulation in TGF‐β superfamily signaling. FASEB J. 13, 2105–2124 (1999)