{PDOC51256}
{PS51256; GS}
{BEGIN}
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* GS domain profile *
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Transforming growth  factor  beta  (TGF-beta) is a member of a large family of
secreted growth  factors  of  central importance in eukaryotic development and
homeostasis. Members of this family, which includes the activins, inhibins and
bone morphogenic  proteins  (BMPs),  bind  to  receptors  that  consist of two
transmembrane serine/threonine (Ser/Thr) kinases called the type I and type II
receptors (TbetaR-I and TbetaR-II, respectively). TbetaR-II activates TbetaR-I
upon formation  of the ligand receptor complex by multiply phosphorylating the
GS domain,  a  short (~30 residues), highly conserved regulatory sequence just
N-terminal to  the  kinase domain on the cytoplasmic side of the receptor. The
GS domain  is  found  only  in the type I receptor family and is named for the
TTSGSGSG sequence at its core. At least three, and perhaps four to five of the
serines and  threonines  in  the  GS  domain,  must be phosphorylated to fully
activate TbetaR-1 [1].

The GS  domain  forms  a  helix-loop-helix  structure  in  which  the sites of
activating phosphorylation  are  situated  in  the  loop  (the  GS  loop) (see
<PDB:1B6C>). One  key  role for phosphorylation is to block the adoption of an
inactivating configuration by the GS domain [2].

The profile we developed covers the entire GS domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: October 2006 / First entry.

[ 1] Huse M., Muir T.W., Xu L., Chen Y.-G., Kuriyan J., Massague J.
     "The TGF beta receptor activation process: an inhibitor- to
     substrate-binding switch."
     Mol. Cell 8:671-682(2001).
     PubMed=11583628
[ 2] Huse M., Chen Y.-G., Massague J., Kuriyan J.
     "Crystal structure of the cytoplasmic domain of the type I TGF beta
     receptor in complex with FKBP12."
     Cell 96:425-436(1999).
     PubMed=10025408

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