Transforming growth factor β signaling mediators and modulators

TY - JOUR

T1 - Transforming growth factor β signaling mediators and modulators

AU - Zimmerman, Cole M.

AU - Padgett, Richard W.

N1 - Funding Information: The work in the authors' laboratory is supported by grants from the NIH and DOD.

PY - 2000/5/16

Y1 - 2000/5/16

N2 - Transforming growth factor β is a multi-functional growth and differentiation factor responsible for regulating many diverse biological processes in both vertebrate and invertebrate species. Among the most dramatic of TGFβ's effects are those associated with specification of cell fates during development and inhibition of cell cycle progression. The core TGFβ signaling pathway has now been described using a synergistic combination of genetic and biochemical approaches. Transmembrane receptors with intrinsic protein serine kinase activity bind ligand in the extracellular milieu and then phosphorylate intracellular proteins known as Smads. Phosphorylated Smads form heterooligomers and translocate into the nucleus where they can modulate transcriptional responses. More recent studies indicate that many other proteins serve as modulators of Smad activity, and utimately define specific cellular responses to TGFβ. Here we describe both the simplistic core TGFβ signaling pathway and the growing number of proteins that impinge on this pathway at the level of Smad function to either enhance or inhibit TGFβ responses Copyright (C) 2000 Elsevier Science B.V.

AB - Transforming growth factor β is a multi-functional growth and differentiation factor responsible for regulating many diverse biological processes in both vertebrate and invertebrate species. Among the most dramatic of TGFβ's effects are those associated with specification of cell fates during development and inhibition of cell cycle progression. The core TGFβ signaling pathway has now been described using a synergistic combination of genetic and biochemical approaches. Transmembrane receptors with intrinsic protein serine kinase activity bind ligand in the extracellular milieu and then phosphorylate intracellular proteins known as Smads. Phosphorylated Smads form heterooligomers and translocate into the nucleus where they can modulate transcriptional responses. More recent studies indicate that many other proteins serve as modulators of Smad activity, and utimately define specific cellular responses to TGFβ. Here we describe both the simplistic core TGFβ signaling pathway and the growing number of proteins that impinge on this pathway at the level of Smad function to either enhance or inhibit TGFβ responses Copyright (C) 2000 Elsevier Science B.V.

KW - Receptor serine kinases

KW - Signal transduction

KW - Smads

KW - Transcription factors

KW - Tumor suppressors

UR - http://www.scopus.com/inward/record.url?scp=0034673972&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034673972&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/S0378-1119(00)00162-1

DO - https://doi.org/10.1016/S0378-1119(00)00162-1

M3 - Review article

C2 - 10831835

SN - 0378-1119

VL - 249

SP - 17

EP - 30

JO - Gene

JF - Gene

IS - 1-2

ER -