Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Stathmin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed2006

Protein expression profiling identifies maspin and stathmin as potential biomarkers of adenoid cystic carcinoma of the salivary glands.

Adenoid cystic carcinoma (ACC) is one of the most common malignant tumors of the salivary glands. It tends to grow slowly but is associated with a poor prognosis compared to other malignant salivary gland tumors. To identify specific markers of ACC, we examined protein expression profiling in ACC xenograft and normal salivary glands (NSG) using fluorescent 2-dimensional differential in-gel electrophoresis (2-D-DIGE), an emerging technique for comparative proteomics, that improves the reproducibility and reliability of differential protein expression analysis between the samples. To identify the proteins, matrix-assisted laser desorption/ionization time-of-flight peptide mass fingerprinting was carried out. Using these strategies, we detected 4 upregulated proteins and 5 downregulated proteins in ACC xenograft. Maspin and stathmin were selected for further analyses. Western blotting and immunohistochemical staining showed a higher expression of these proteins in ACC xenograft and clinical ACC tissue compared to NSG. Furthermore, Expression of these proteins was correlated with the histologic grading of ACC (n = 10). Therefore, our data indicate that maspin and stathmin may be not only useful biomarkers of ACC but also markers of biologic behavior in this tumor.

Animals↗
PubMed1999

Bistratene A induces a microtubule-dependent block in cytokinesis and altered stathmin expression in HL60 cells.

Bistratene A is a cyclic polyether which affects cell cycle progression and can induce phosphorylation of cellular proteins. Treatment of HL60 cells with 100 ng/ml bistratene A was found to inhibit cytokinesis but had no effect on DNA synthesis and nuclear division. Consequently, bistratene A-treated cells became polyploid and multinucleate. In association with the development of this phenotype, the cytoplasmic protein stathmin was biphasically phosphorylated and levels of expression were doubled. Immunostaining of binucleate cells (bistratene A for 24 h) revealed increased alpha-tubulin localization where the cleavage furrow might be expected to form, i.e., along the equatorial plane. Treatment of these binucleate cells with the microtubule depolymerizing agent nocadazole promoted cleavage furrow formation and partially ameliorated the bistratene A-induced block in cell division. These findings implicate the polymerization status of microtubules and stathmin function in the regulation of cytokinesis.

Acetamides↗
PubMed1993

The phosphorylation of stathmin by MAP kinase.

Stathmin, a ubiquitous cytosolic phosphoprotein which may play a role in integrating the effects of diverse signals regulating proliferation, differentiation and other cell functions, was found to be phosphorylated rapidly and stoichiometrically by mitogen-activated protein (MAP) kinase in vitro. Ser-25 was identified as the major site and Ser-38 as a minor site of phosphorylation, while the p42 and p44 isoforms of MAP kinase were the only significant stathmin kinases detected in PC12 cells after stimulation by nerve growth factor (NGF). The results suggest that MAP kinases are the enzymes responsible for increasing the level of phosphorylation of Ser-25, which has been observed previously in PC12 cells following stimulation by NGF.

Amino Acid Sequence↗
PubMed2004

Clustering of cellular prion protein induces ERK1/2 and stathmin phosphorylation in GT1-7 neuronal cells.

The physiological role of the prion protein is largely unknown. Here, clustering of prion at the surface of GT1-7 cells was observed upon anti-prion antibody treatments. This clustering was associated with a rapid and transient phosphorylation of the mitogen activated protein kinases (MAPKs) extracellular receptor kinases 1 and 2 (ERK1/2), and also of the microtubule-destabilizing protein stathmin at serine 16. The specificity of this antibody-mediated activation was ascertained by its inhibition by prion small interfering RNA. The phosphorylation of ERK1/2 but not that of stathmin was abolished by the MAPK/ERK kinase 1 inhibitor U0126, whereas both signaling pathways were blocked by the specific inhibitor of the epidermal growth factor receptor AG1478, suggesting the likely recruitment of this receptor upon prion clustering.

Animals↗
PubMed1997

Phosphorylation regulates the microtubule-destabilizing activity of stathmin and its interaction with tubulin.

Stathmin is a regulator of microtubule dynamics which undergoes extensive phosphorylation during the cell cycle as well as in response to various extracellular factors. Four serine residues are targets for protein kinases: Ser-25 and Ser-38 for proline-directed kinases such as mitogen-activated protein kinase and cyclin-dependent protein kinase, and Ser-16 and Ser-63 for cAMP-dependent protein kinase. We studied the effect of phosphorylation on the microtubule-destabilizing activity of stathmin and on its interaction with tubulin in vitro. We show that triple phosphorylation on Ser-16, Ser-25, and Ser-38 efficiently inhibits its activity and prevents its binding to tubulin.

Animals↗
PubMed2000

The 4 A X-ray structure of a tubulin:stathmin-like domain complex.

Phosphoproteins of the stathmin family interact with the alphabeta tubulin heterodimer (tubulin) and hence interfere with microtubule dynamics. The structure of the complex of GDP-tubulin with the stathmin-like domain of the neural protein RB3 reveals a head-to-tail assembly of two tubulins with a 91-residue RB3 alpha helix in which each copy of an internal duplicated sequence interacts with a different tubulin. As a result of the relative orientations adopted by tubulins and by their alpha and beta subunits, the tubulin:RB3 complex forms a curved structure. The RB3 helix thus most likely prevents incorporation of tubulin into microtubules by holding it in an assembly with a curvature very similar to that of the depolymerization products of microtubules.

Amino Acid Sequence↗
PubMed2004

Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain.

Microtubules are cytoskeletal polymers of tubulin involved in many cellular functions. Their dynamic instability is controlled by numerous compounds and proteins, including colchicine and stathmin family proteins. The way in which microtubule instability is regulated at the molecular level has remained elusive, mainly because of the lack of appropriate structural data. Here, we present the structure, at 3.5 A resolution, of tubulin in complex with colchicine and with the stathmin-like domain (SLD) of RB3. It shows the interaction of RB3-SLD with two tubulin heterodimers in a curved complex capped by the SLD amino-terminal domain, which prevents the incorporation of the complexed tubulin into microtubules. A comparison with the structure of tubulin in protofilaments shows changes in the subunits of tubulin as it switches from its straight conformation to a curved one. These changes correlate with the loss of lateral contacts and provide a rationale for the rapid microtubule depolymerization characteristic of dynamic instability. Moreover, the tubulin-colchicine complex sheds light on the mechanism of colchicine's activity: we show that colchicine binds at a location where it prevents curved tubulin from adopting a straight structure, which inhibits assembly.

Amino Acid Sequence↗
PubMed2000

Rac/Cdc42 and p65PAK regulate the microtubule-destabilizing protein stathmin through phosphorylation at serine 16.

We have identified a rapid protein phosphorylation event at residue serine 16 of stathmin using two-dimensional gel electrophoresis coupled to matrix-assisted laser desorption/ionization mass spectrometry in combination with post-source decay analysis, which is induced by the epidermal growth factor receptor. Phosphorylation is specifically mediated by the small GTPases Rac and Cdc42 and their common downstream target, the serine/threonine kinase p65PAK. Both GTPases have previously been shown to regulate the dynamics of actin polymerization. Because stathmin destabilizes microtubules, and this process is inhibited by phosphorylation at residue 16, Rac and Cdc42 can potentially regulate both F-actin and microtubule dynamics.

Cell Line↗
PubMed2001

Increased expression of synaptophysin and stathmin mRNAs after methamphetamine administration in rat brain.

The rearrangement of neural networks associated with the behavioral sensitization induced by psychostimulants is poorly understood. We have investigated the effect of methamphetamine (METH) administration on the mRNA levels of three different classes of plasticity-related genes in the rat brain. The expression of synaptophysin mRNA increased 20-40% in the nucleus accumbens, prefrontal and temporal cortices, 1-24 h after acute METH administration, and that of stathmin mRNA increased about 20% in the prefrontal cortex 1 h later. They did not change after subchronic administration. The level of alpha-tubulin mRNA was constant. Therefore, synaptophysin and stathmin play an important role in the neural plastic changes involved in the early induction process of METH-induced sensitization, but not in the later maintenance process.

Animals↗
PubMed2004

Stathmin-tubulin interaction gradients in motile and mitotic cells.

The spatial organization of the microtubule cytoskeleton is thought to be directed by steady-state activity gradients of diffusible regulatory molecules. We visualized such intracellular gradients by monitoring the interaction between tubulin and a regulator of microtubule dynamics, stathmin, using a fluorescence resonance energy transfer (FRET) biosensor. These gradients were observed both during interphase in motile membrane protrusions and during mitosis around chromosomes, which suggests that a similar mechanism may contribute to the creation of polarized microtubule structures. These interaction patterns are likely to reflect phosphorylation of stathmin in these areas.

Animals↗
PubMed1994

Leydig tumor cell protein phosphorylated in response to stimulation with choriogonadotropin or epidermal growth factor is identified as stathmin.

Although hCG and mouse epidermal growth factor activate different signaling systems in a clonal strain of Leydig tumor cells (designated MA-10), both compounds are capable of increasing steroidogenesis, decreasing transcription of the LH/CG receptor gene, and attenuating adenylyl cyclase. We have recently identified a 21-kilodalton protein (p21) that is a potential intermediary in the actions of mouse epidermal growth factor and hCG. Characterization of p21 revealed similarities to stathmin, a ubiquitous phosphoprotein whose phosphorylation is associated with diverse second messenger pathways. Using two different experimental approaches, Western blotting and immunoprecipitation, we present data that identify p21 as stathmin.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Mass spectrometric characterization of stathmin isoforms separated by 2D PAGE.

In proteome analysis, the determination of the phosphorylation status of proteins and protein isoforms, which have been separated by two-dimensional polyacrylamide gel electrophoresis (2D PAGE), is of prime importance in addition to their identification. In this study, the extent to which such information can be directly extracted from the mass spectrometric data used for identification was evaluated. By searching for metastable peaks which are characteristic for loss of phosphoric acid, the Ser-phosphorylated peptides were identified with a high success rate in reflector matrix-assisted laser desorption/ionization (MALDI) mass maps of in-gel digested proteins. Furthermore, by employing a double enzymatic strategy using trypsin and Glu-C in parallel, improved sequence coverage and additional separation of the potential phosphorylation sites of the isoforms were achieved. The precise location of the modified sites within an identified phosphopeptide was obtained by submitting the corresponding molecular ions directly to nano-electrospray tandem mass spectrometric analysis. In this way the detailed phosphorylation status of six isomers of stathmin separated by 2D PAGE was determined. Two of these six isomers were phosphorylated at all four known sites (serines 15, 24, 37 and 62) and were probably derived from the previously reported alpha and beta forms, which differ by a yet unknown modification. In addition, isomers phosphorylated at serines 15, 24 and 37, serines 24, 37 and 62, serines 24 and 37 and serine 37 only were characterized.

Amino Acid Sequence↗
PubMed1991

Stathmin: a relay phosphoprotein for multiple signal transduction?

Stathmin is a ubiquitous, phylogenetically conserved protein present in the cytoplasm of cells in a variety of unphosphorylated and phosphorylated forms. Its expression and phosphorylation are regulated throughout development and in response to extracellular signals regulating cell proliferation, differentiation and functions. The overall pattern of its molecular forms reflects the activation of corresponding second messenger pathways. This phosphoprotein is therefore a good candidate as a general relay in signal transduction, possibly integrating diverse signals of the cell's environment.

Amino Acid Sequence↗
PubMed2003

Fluorescence correlation spectroscopy analysis of the dynamics of tubulin interaction with RB3, a stathmin family protein.

We have used fluorescence correlation spectroscopy to analyze the interaction of GTP-tubulin with rhodamine-labeled RB3, a neural protein of the stathmin family, and to determine the kinetic pathway of the association process. RB3 displayed slow association-dissociation kinetics with tubulin depending on the square of the tubulin concentration. The values of the apparent association and dissociation rate constants of the complex of two tubulin dimers and RB3 are determined to be (3.52+/-0.14)x10(-3) micro;M(-2)/s and (1.9+/-0.6)x10(-3) s(-1) respectively. The value of the equilibrium dissociation constant for the first tubulin-RB3 interaction is estimated to be >or=7 microM at 20 degrees C.

Amino Acid Sequence↗
PubMed1989

Intracellular substrates for extracellular signaling. Characterization of a ubiquitous, neuron-enriched phosphoprotein (stathmin).

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 approximately 19,000, pI approximately 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 degrees 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).

Animals↗
PubMed1998

Neuronal activity induction of the stathmin-like gene RB3 in the rat hippocampus: possible role in neuronal plasticity.

Synaptic activity induces a rapid transcriptional response that is essential for the establishment of long-term neuronal plasticity. Using a differential cloning technique, we have identified a gene induced by seizure activity in the brain as RB3. RB3 is a recently cloned gene belonging to the stathmin family of phosphoproteins. Like SCG10, RB3 is brain-specific, although in situ hybridization results show that the expression of RB3 is more ubiquitous than is that of SCG10. Using genomic DNA sequencing, we show that the 27 amino acid sequence unique to the RB3" transcript is encoded by an alternatively spliced exon, exon 2'. Using a peptide antibody raised against exon 2' to detect RB3" and an anti-Flag antibody to detect an epitope-tagged version of RB3, we show that both proteins are localized to the Golgi apparatus of transfected COS7 cells. Of particular interest, RB3 mRNA, but not SCG10 mRNA, is rapidly induced in the dentate gyrus granule layer of the hippocampus after electrically induced seizure activity as well as stimuli leading to long-term potentiation (LTP). In addition, RB3 mRNA is induced in pheochromocytoma (PC12) cells treated with 250 ng/ml NGF. These results suggest that RB3 may play a role in activity-induced neuronal plasticity and neuronal differentiation.

Alternative Splicing↗
PubMedDate not supplied

Persistent growth of BALB/C mouse plasmacytoma and human myeloma cell lines in the presence of phorbol myristate acetate is associated with continued expression of Lap18 (stathmin).

Lap18 is a highly conserved cytosolic protein that is expressed in dividing cells. Data from a number of studies show that a range of cell lines and mitogen-stimulated normal cells cultured in PMA phosphorylate and subsequently down-regulate Lap18. This has been found to be associated with growth arrest, although it is not clear that these events are causally related. In the present study we confirm that the HL60 promyelocytic leukemia and K562 erythroleukemia cell lines, when cultured with PMA, behave in this manner. This was not the case for any of five mouse plasmacytoma cell lines and six lines derived from patients with multiple myeloma or plasma cell leukemia. All of these lines contain Lap18, although the level of this protein in the mouse but not the human plasmacytoma cell-line cells is relatively low. All the neoplastic plasma cell-line cells phosphorylate Lap18 on culture with PMA, but this does not induce growth arrest nor result in down-regulation of Lap18 expression. Further experiments are required to test whether there is a mechanistic relationship between the continued growth of plasmacytoma cell lines and their failure to down-regulate Lap18 on culture in PMA.

Animals↗