TY - JOUR
T1 - Tyrosine phosphorylation of missing in metastasis protein is implicated in platelet-derived growth factor-mediated cell shape changes
AU - Wang, Ying
AU - Zhou, Kang
AU - Zeng, Xianchun
AU - Lin, Jinxiu
AU - Zhan, Xi
PY - 2007/3/2
Y1 - 2007/3/2
N2 - Missing in metastasis gene, or MTSS1, encodes an intracellular protein that is implicated in actin cytoskeleton reorganization and often down-regulated in certain types of tumor cells. In response to platelet-derived growth factor (PDGF), green fluorescent protein (GFP)-tagged murine Mtss1 (Mtss1-GFP) underwent redistribution from the cytoplasm to dorsal membrane ruffles along with phosphorylation at tyrosine residues in a time-dependent manner. Tyrosine phosphorylation of Mtss1-GFP was also elevated in cells where an oncogenic Src was activated but severely impaired in Src knock-out cells or cells treated with Src kinase inhibitor PP2. Mutagenesis analysis has revealed that phosphorylation occurs at multiple sites, including tyrosine residues Tyr-397 and Tyr-398. Mutation at both Tyr-397 and Tyr-398 abolished the PDGF-mediated tyrosine phosphorylation. Furthermore, recombinant Mtss1 protein was phosphorylated by recombinant Src in a manner dependent on Tyr-397 and Tyr-398. Efficient tyrosine phosphorylation of Mtss1 in response to PDGF also involves a coiled-coil domain, which is essential for a proper distribution to the cell leading edge and dorsal ruffles. Interestingly, overexpression of wild type Mtss1-GFP promoted the PDGF-induced dorsal ruffling, whereas overexpression of a mutant deficient in phosphorylation at Tyr-397 and Tyr-398 or a mutant with deletion of the coiled-coil domain impaired the formation of dorsal ruffles. These data indicate that Mtss1 represents a novel signaling pathway from PDGF receptor to the actin cytoskeleton via Srcrelated kinases.
AB - Missing in metastasis gene, or MTSS1, encodes an intracellular protein that is implicated in actin cytoskeleton reorganization and often down-regulated in certain types of tumor cells. In response to platelet-derived growth factor (PDGF), green fluorescent protein (GFP)-tagged murine Mtss1 (Mtss1-GFP) underwent redistribution from the cytoplasm to dorsal membrane ruffles along with phosphorylation at tyrosine residues in a time-dependent manner. Tyrosine phosphorylation of Mtss1-GFP was also elevated in cells where an oncogenic Src was activated but severely impaired in Src knock-out cells or cells treated with Src kinase inhibitor PP2. Mutagenesis analysis has revealed that phosphorylation occurs at multiple sites, including tyrosine residues Tyr-397 and Tyr-398. Mutation at both Tyr-397 and Tyr-398 abolished the PDGF-mediated tyrosine phosphorylation. Furthermore, recombinant Mtss1 protein was phosphorylated by recombinant Src in a manner dependent on Tyr-397 and Tyr-398. Efficient tyrosine phosphorylation of Mtss1 in response to PDGF also involves a coiled-coil domain, which is essential for a proper distribution to the cell leading edge and dorsal ruffles. Interestingly, overexpression of wild type Mtss1-GFP promoted the PDGF-induced dorsal ruffling, whereas overexpression of a mutant deficient in phosphorylation at Tyr-397 and Tyr-398 or a mutant with deletion of the coiled-coil domain impaired the formation of dorsal ruffles. These data indicate that Mtss1 represents a novel signaling pathway from PDGF receptor to the actin cytoskeleton via Srcrelated kinases.
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U2 - 10.1074/jbc.M608448200
DO - 10.1074/jbc.M608448200
M3 - Article
C2 - 17224454
AN - SCOPUS:34147108621
SN - 0021-9258
VL - 282
SP - 7624
EP - 7631
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 10
ER -