Regulation of Dictyostelium protein-tyrosine phosphatase-3 (PTP3) through osmotic shock and stress stimulation and identification of pp130 as a PTP3 substrate.
Osmotic shock and growth-medium stimulation of Dictyostelium cells results in rapid cell rounding, a reduction in cell volume, and a rearrangement of the cytoskeleton that leads to resistance to osmotic shock. Osmotic shock induces the activation of guanylyl cyclase, a rise in cGMP mediating the phosphorylation of myosin II, and the tyrosine phosphorylation of actin and the approximately 130-kDa protein (p130). We present data suggesting that signaling pathways leading to these different responses are, at least in part, independent. We show that a variety of stresses induce the Ser/Thr phosphorylation of the protein-tyrosine phosphatase-3 (PTP3). This modification does not alter PTP3 catalytic activity but correlates with its translocation from the cytosol to subcellular structures that co-localize to endosomal vesicles. This translocation is independent of PTP3 activity. Mutation of the catalytically essential Cys to a Ser results in inactive PTP3 that forms a stable complex with tyrosine-phosphorylated p130 (pp130) in vivo and in vitro, suggesting that PTP3 has a substrate specificity for pp130. The data suggest that stresses activate several interacting signaling pathways controlled by Ser/Thr and Tyr phosphorylation, which, along with the activation of guanylyl cyclase, mediate the ability of this organism to respond to adverse changes in the external environment.
Gamper
M
M
Department of Biology, Center for Molecular Genetics, University of California, San Diego, La Jolla, California 92093-0634, USA.
Kim
E
E
Howard
P K
PK
Ma
H
H
Hunter
T
T
Firtel
R A
RA
D000199:Actins / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002384:Catalysis; D006152:Cyclic GMP / Q000378:metabolism; D004023:Dictyostelium / Q000201:enzymology*; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D009997:Osmotic Pressure; D018384:Oxidative Stress; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism
D000199:Actins; D047908:Intracellular Signaling Peptides and Proteins; D015800:Protozoan Proteins; D014443:Tyrosine; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D006162:Guanylate Cyclase; D006152:Cyclic GMP