Species specificity and organ, cellular and subcellular localization of the 100 kDa Ras GTPase activating protein.
A p100-GAP isoform, generated by an alternative splicing mechanism that eliminates the 180 hydrophobic amino acids at the amino terminus of p120-GAP, has been described in human placenta, in addition to the known p120GAP and neurofibromin. This p100-GAP possesses full Ras-GTPase stimulating activity. p120-GAP is ubiquitously localized in the cytosol while the localization of p100-GAP is unknown. Here we have explored the precise localization of p100-GAP and show that p100-GAP is present only in extracts of primate placenta. It is abundant in both human and Maccaca Rhesus placentae, where it is present in far larger amounts than p120-GAP. The p100-GAP is species-specific since it was not detected in the placenta of pig, sheep, mouse or rat. p100-GAP was also found to be organ-specific, since it was not detectable in organs other than the placenta. In this connection, we substantiated our previous finding that p100-GAP is mainly localized in the trophoblasts. Both subcellular trophoblast fractionation and immunofluorescence analyses showed that this protein was distributed between the cytosol, plasma membrane and a fraction bound to the nucleus, but not inside it. This highly restrictive specificity of p100-GAP localization in relation to species, organ and cell type, confirms the extreme singularity of this protein, and strongly suggests a particular specific function in the trophoblast.
Mollat
P
P
Unité 245 INSERM, Hôpital Saint-Antoine, Paris, France.
Fournier
A
A
Yang
C Z
CZ
Alsat
E
E
Zhang
Y
Y
Evain-Brion
D
D
Grassi
J
J
Thang
M N
MN
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D005455:Fluorescent Antibody Technique; D020690:GTPase-Activating Proteins; D006801:Humans; D008252:Macaca fascicularis; D008253:Macaca mulatta; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010920:Placenta / Q000737:chemistry; D011247:Pregnancy; D011506:Proteins / Q000032:analysis*; D051381:Rats; D012756:Sheep; D013045:Species Specificity; D014327:Trophoblasts / Q000737:chemistry; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D011506:Proteins; D020703:ras GTPase-Activating Proteins