Specificity, diversity, and regulation in TGF-beta superfamily signaling.
Transforming growth factor-beta (TGF-beta) 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-beta superfamily (with approximately 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-beta 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-beta superfamily signaling.
Piek
E
E
Ludwig Institute for Cancer Research, Box 595, S-75124 Uppsala, Sweden.
Heldin
C H
CH
Ten Dijke
P
P
D000818:Animals; D006801:Humans; D020033:Protein Isoforms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D017978:Receptors, Growth Factor / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D020033:Protein Isoforms; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases