Stathmin is a major phosphoprotein and cyclic AMP-dependent protein kinase substrate in mouse brain neurons but not in astrocytes in culture: regulation during ontogenesis.
Stathmin is a ubiquitous soluble protein (Mr approximately 19,000; pI approximately 6.2-5.5) whose phosphorylation is associated with the intracellular mechanisms involved in the regulations of cell differentiation and functions by extracellular effectors. It is present in various tissues and cell types and has several nonphosphorylated and increasingly phosphorylated forms, and it is particularly abundant in brain. Very high concentrations of stathmin were also detected in mouse embryo striatal neurons grown in primary culture, whereas stathmin was barely detectable in astrocytes from the same source. Stathmin appeared in neurons as a major substrate for protein phosphorylation and, in particular, for the cyclic AMP (cAMP)-dependent protein kinase, because its phosphorylation was stimulated by cAMP in cell-free preparations and in intact cells by forskolin, a potent activator of adenylate cyclase. During brain ontogenesis, stathmin was first detected at embryonic day 12; its concentration increased until birth and then decreased from postnatal day 10 to adulthood. In parallel, its molecular forms shifted from the least phosphorylated to the more phosphorylated ones. This result may reflect the evolution of the activity of stathmin during development and the subsequent maturation of the brain. In conclusion, our results substantiate the likely role of stathmin as an intracellular relay of extracellular regulations, as they point out its specific importance related to neuronal functions and brain differentiation.
Chneiweiss
H
H
INSERM U153-CNRS URA614, Paris, France.
Beretta
L
L
Cordier
J
J
Boutterin
M C
MC
Glowinski
J
J
Sobel
A
A
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology / Q000196:embryology; D000242:Cyclic AMP / Q000494:pharmacology*; D015180:Electrophoresis, Gel, Two-Dimensional; D051379:Mice; D008868:Microtubule Proteins; D009474:Neurons / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D050777:Stathmin
D008868:Microtubule Proteins; D010750:Phosphoproteins; D050777:Stathmin; C493994:Stmn1 protein, mouse; D005576:Colforsin; D000242:Cyclic AMP; D011494:Protein Kinases; D015056:1-Methyl-3-isobutylxanthine