Specificity, diversity, and regulation in TGF-beta superfamily signaling

Transforming growth factor-beta (TGF-beta) superfamily members are multifun ctional cell-cell signaling proteins that play pivotal roles in tissue home ostasis and development of multicellular animals, They mediate their pleiot ropic effects from membrane to nucleus through distinct combinations of typ e I and type II serine/threonine kinase receptors and their downstream effe cters, known as Smad proteins. Certain Smads, termed receptor-regulated Sma ds, become phosphorylated by activated type I receptors and form heteromeri c complexes with a common-partner Smad4, which translocates into the nucleu s to control gene transcription, In addition to these signal transducing Sm ads, inhibitory Smads have been identified that inhibit the activation of r eceptor-regulated Smads, In contrast to the still growing TGF-beta superfam ily (with similar to 30 members in mammals), relatively few type I and type II receptors as well as Smads have been identified. We will focus on recen t insights into the molecular mechanisms by which signaling specificity bet ween different TGF-beta superfamily members is achieved and regulated, and how a single family member can elicit a broad scala of biological responses .