Intracellular Substrates for Extracellular Signaling

• Published in: The Journal of biological chemistry 1989-03, Vol.264 (7), p.3765-3772
• Main Authors: Sobel, A, Boutterin, M C, Beretta, L, Chneiweiss, H, Doye, V, Peyro-Saint-Paul, H
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)84915-3

We previously identified (Sobel, A., and Tashjian, A. H., Jr. (1983) J. Biol. Chem. 258, 10312-10324) a group of cytoplasmic proteins whose phosphorylation could be related to the regulation by extracellular effectors of cells as different as pituitary and muscle cells. Among these phosphoproteins, proteins “7” and “8” (Mr ≈ 19,000, pI ≈ 5.8-6.0), that we now designate P1 and P2, are very abundant in rat brain. Partial purification of these proteins was therefore achieved after 100 ° C precipitation of a rat brain-soluble fraction and further fractionation of the supernatant by ion exchange chromatography. Several related non-phosphorylated (N1, N2) and phosphorylated (P3) proteins were also identified in the heat-resistant supernatant. Antisera raised against P2 extracted from nitrocellulose blots of semipreparative two-dimensional gels recognized all the proteins N1, N2, P1, P2, and P3, confirming that they belong to the same protein family, and suggesting that they are likely various forms of a single protein core. The same protein could be detected biochemically and immunologically at various concentrations in all the tissues or cell types from diverse mammalian and nonmammalian species tested. Together with our previous data relating its phosphorylation to the regulation of the proliferation, differentiation, and/or the functions of the cells considered, this observation leads us to suggest that it might be an ubiquitous regulatory phosphoprotein playing the role of an intracellular “relay” for extracellular signals, after their binding to specific membrane receptors and the generation of second messengers. We propose to name this protein stathmin, from the greek “stathmos” (relay).