Localization of SV40 T antigen in mitotic cells by an immunoperoxidase method

The immunoperoxidase technique has clearly demonstrated that SV 40 T antigen is dissociated from the chromosomes in mitotic cells, and massive transport of T antigen from the cytoplasm to the nucleus appears to take place during or immediately after the telophase.     

Effects of penfluridol of dopamine-sensitive adenylate cyclase in corpus striatum and substantia nigra of rats.

Penfluridol, a neuroleptic with diphenylbutyl piperidine structure, blocked the dopamine-sensitive adenylate cyclase in homogenates of corpus striatum and substantia nigra of rats, probably by a competitive antagonism versus dopamine.     

Levels of alpha1-antitrypsin in the spring and autumn seasons.

In a group of 84 pairs of 11-year-old children of both sexes, the level of the alpha1-antitrypsin (alpha1-AT) were ascertained in the autumn and spring. Although the mean levels of alpha1-AT in the two seasons hardly differed, the highly significant seasonal changes in the distribution curves of alpha1-AT values were noted in boys, whereas the levels showed higher stability in girls.     

HCO-3-ATPase activity distribution in rat liver cell fractions prepared by zonal centrifugation.

Plasma membrane sheets prepared by zonal centrifugation of a premicrosomal pellet obtained from a rat liver homogenate are devoid of HCO-3-ATPase activity. Since the microsomal fraction is also lacking in this ATPase activity, it can be concluded that the HCO-3-ATPase is not involved in the secretion of HCO-3 into bile.     

Gastric mucus effusion elicited by oral copper compounds: potential anti-ulcer activity.

In rats, both Cu(I) and Cu(II) show an irritancy profile not shared with Cu degrees or Zn(II) or Ni(II). The gastric response to Cu(II), i.e. copius fluid and mucus secretion, can protect the stomach from the acute ulcerative effects of aspirin or physical stress administered subsequently.     

Structure of Cdc42 in complex with the GTPase-binding domain of the 'Wiskott-Aldrich syndrome' protein.

The Rho-family GTP-hydrolysing proteins (GTPases), Cdc42, Rac and Rho, act as molecular switches in signalling pathways that regulate cytoskeletal architecture, gene expression and progression of the cell cycle. Cdc42 and Rac transmit many signals through GTP-dependent binding to effector proteins containing a Cdc42/Rac-interactive-binding (CRIB) motif. One such effector, the Wiskott-Aldrich syndrome protein (WASP), is postulated to link activation of Cdc42 directly to the rearrangement of actin. Human mutations in WASP cause severe defects in haematopoletic cell function, leading to clinical symptoms of thrombocytopenia, immunodeficiency and eczema. Here we report the solution structure of a complex between activated Cdc42 and a minimal GTPase-binding domain (GBD) from WASP. An extended amino-terminal GBD peptide that includes the CRIB motif contacts the switch I, beta2 and alpha5 regions of Cdc42. A carboxy-terminal beta-hairpin and alpha-helix pack against switch II. The Phe-X-His-X2-His portion of the CRIB motif and the alpha-helix appear to mediate sensitivity to the nucleotide switch through contacts to residues 36-40 of Cdc42. Discrimination between the Rho-family members is likely to be governed by GBD contacts to the switch I and alpha5 regions of the GTPases. Structural and biochemical data suggest that GBD-sequence divergence outside the CRIB motif may reflect additional regulatory interactions with functional domains that are specific to individual effectors.     

Integrin cytoplasmic tyrosine motif is required for outside-in alphaIIbbeta3 signalling and platelet function.

Integrins not only bind adhesive ligands, they also act as signalling receptors. Both functions allow the integrin alphaIIbbeta3 to mediate platelet aggregation. Platelet agonists activate alphaIIbbeta3 (inside-out signalling) to allow the binding of soluble fibrinogen. Subsequent platelet aggregation leads to outside-in alphaIIbbeta3 signalling, which results in calcium mobilization, tyrosine phosphorylation of numerous proteins including beta3 itself, increased cytoskeletal reorganisation and further activation of alphaIIbbeta3. Thus, outside-in signals enhance aggregation, although the mechanisms and functional consequences of specific signalling events remain unclear. Here we describe a mouse that expresses an alphaIIbbeta3 in which the tyrosines in the integrin cytoplasmic tyrosine motif have been mutated to phenylalanines. These mice are selectively impaired in outside-in alphaIIbbeta3 signalling, with defective aggregation and clot-retraction responses in vitro, and an in vivo bleeding defect which is characterized by a pronounced tendency to rebleed. These data provide evidence for an important role of outside-in signalling in platelet physiology. Furthermore, they identify the integrin cytoplasmic tyrosine motif as a key mediator of beta-integrin signals and a potential target for new therapeutic agents.