Human Molecular Genetics, Vol 8, 2239-2245, Copyright © 1999 by Oxford University Press
NC Jones, PG Farlie, J Minichiello and DF Newgreen
Treacher Collins syndrome (TCS) is an autosomal dominant craniofacial
disorder involving the mid and lower face and, in particular, the tissues
affected arise solely from embryonic branchial arches I and II. TCOF1, the
gene involved in TCS, has been cloned and although the function of the
encoded protein, treacle, has not yet been established, it exhibits peak
expression in the branchial arches. Treacle contains a series of repeating
units of acidic and basic residues, which are predicted to contain putative
casein kinase II (CKII) and protein kinase C (PKC) phosphorylation site
motifs. In addition, treacle has weak homology to two
phosphorylation-dependent nucleolar proteins, which shuttle between the
cytoplasm and nucleolus. Based on these observations, phosphorylation of
treacle may be important for its function. In this study, GST-treacle
fusion peptides were constructed using particular TCOF1 exons that
contained potential CKII and PKC phosphorylation sites. These were used as
substrates in in vitro kinase assays and showed that treacle fusion
peptides can be phosphorylated by the appropriate kinases. Furthermore,
using tissue extracts we have demonstrated that in avian embryonic
branchial arches I and II there is a kinase activity that can phosphorylate
treacle peptides that is consistent with CKII site recognition. This
activity coincides with the reported high expression of treacle in these
tissues at early developmental stages and declines later in development.
ARTICLES
Detection of an appropriate kinase activity in branchial arches I and II that coincides with peak expression of the Treacher Collins syndrome gene product, treacle
Murdoch Institute, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia
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