TY - JOUR
T1 - PKCγ regulates syndecan-2 inside-out signaling during xenopus left-right development
AU - Kramer, Kenneth L.
AU - Barnette, Janet E.
AU - Yost, H. Joseph
N1 - Funding Information:
We thank Bill Bradford, Brandon Burbach, Maureen Condic, Jeff Essner, and David Virshup for helpful suggestions; Mark Mercola for discussions and sharing unpublished observations; and Guido David, Randall Moon, and Ajit Verma for reagents. K.L.K. was supported by a NRSA from NIH/NIHLB. Core facilities are supported by NCI CCSG. This work was supported by grants to H.J.Y. from an NIH/NIHLB SCOR program and the Huntsman Cancer Foundation.
PY - 2002/12/27
Y1 - 2002/12/27
N2 - The transmembrane proteoglycan syndecan-2 cell nonautonomously regulates left-right (LR) development in migrating mesoderm by an unknown mechanism, leading to LR asymmetric gene expression and LR orientation of the heart and gut. Here, we demonstrate that protein kinase C γ (PKCγ) mediates phosphorylation of the cytoplasmic domain of syndecan-2 in right, but not left, animal cap ectodermal cells. Notably, both phosphorylation states of syndecan-2 are obligatory for normal LR development, with PKCγ-dependent phosphorylated syndecan-2 in right ectodermal cells and nonphosphorylated syndecan-2 in left cells. The ectodermal cells contact migrating mesodermal cells during early gastrulation, concurrent with the transmission of LR information. This precedes the appearance of monocilia and is one of the earliest steps of LR development. These results demonstrate that PKCγ regulates the cytoplasmic phosphorylation of syndecan-2 and, consequently, syndecan-2-mediated inside-out signaling to adjacent cells.
AB - The transmembrane proteoglycan syndecan-2 cell nonautonomously regulates left-right (LR) development in migrating mesoderm by an unknown mechanism, leading to LR asymmetric gene expression and LR orientation of the heart and gut. Here, we demonstrate that protein kinase C γ (PKCγ) mediates phosphorylation of the cytoplasmic domain of syndecan-2 in right, but not left, animal cap ectodermal cells. Notably, both phosphorylation states of syndecan-2 are obligatory for normal LR development, with PKCγ-dependent phosphorylated syndecan-2 in right ectodermal cells and nonphosphorylated syndecan-2 in left cells. The ectodermal cells contact migrating mesodermal cells during early gastrulation, concurrent with the transmission of LR information. This precedes the appearance of monocilia and is one of the earliest steps of LR development. These results demonstrate that PKCγ regulates the cytoplasmic phosphorylation of syndecan-2 and, consequently, syndecan-2-mediated inside-out signaling to adjacent cells.
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U2 - 10.1016/S0092-8674(02)01200-X
DO - 10.1016/S0092-8674(02)01200-X
M3 - Article
C2 - 12507425
AN - SCOPUS:0037184611
VL - 111
SP - 981
EP - 990
JO - Cell
JF - Cell
SN - 0092-8674
IS - 7
ER -