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Specificity, diversity, and regulation in TGF-beta superfamily signaling Piek E; Heldin CH; Ten Dijke PFASEB J 1999[Dec]; 13 (15): 2105-24Transforming 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.|*Protein Serine-Threonine Kinases[MESH]|*Receptors, Transforming Growth Factor beta[MESH]|*Signal Transduction[MESH]|Animals[MESH]|Humans[MESH]|Protein Isoforms/metabolism[MESH]|Receptors, Growth Factor/*metabolism[MESH]|Transcription Factors/metabolism[MESH]|Transforming Growth Factor beta/*metabolism[MESH] |
