News & Views

The notion that a transmembrane receptor at the cell surface can somehow reappear as a transcription factor in the nucleus is bound to be controversial. However, there are two reported examples of this. If this hypothesis can withstand the inevitable and necessary battery of additional empirical tests then our understanding of signal transduction needs to move in a new direction.

How are Wnt signals made effective in only the right times and places? New studies of the asymmetrical influences of Wnt signals originating from a source show the importance of differential signal degradation and regulated endocytosis.

Cip/Kip proteins that inhibit cyclin-dependent kinase 2 (Cdk2) restrain the initiation of DNA replication. Degradation of a Xenopus Kip1 orthologue, Xic1, is dependent on its recruitment to replication origins. This ensures that activation of Cdk2 and subsequent initiation of replication is co-ordinately regulated at, and localized to, replication origins.

Phosphoinositides recruit proteins to distinct intracellular membranes. Now, the Phox homology (PX) domain, an evolutionarily conserved protein domain whose function has so far been elusive, has been demonstrated to bind phosphoinositides. The interactions of PX-domain-containing proteins with specific phosphoinositides are critical for cellular activities such as microbial killing and membrane trafficking.

Signals generated by the tyrosine kinase receptor Met elicit a complex biological response including cell dissociation, migration, protection from apoptosis, proliferation and differentiation. Paradoxically, all these are triggered by phosphorylation of a single two-tyrosine motif in the Met receptor tail, docking multiple SH2 signal transducers. The precise amino acid sequence of the motif is an absolute requirement for fulfilling the response, showing that there is specificity in intracellular pathways.

No mutation in the fibroblast-growth-factor receptor-4 (FGFR-4) signalling pathway has so far been associated with either heritable human diseases or cancer. A new study now implicates N-CAM–FGFR-4 signalling in the regulation of tumour-cell–matrix adhesion and in the metastatis of pancreatic β-cell tumours.

Centrosomes define the poles of mitotic spindles, but spindles that lack centrosomes mediate meiotic chromosome segregation in females. Recent studies provide new insight into anastral-spindle assembly, and indicate that a conserved protein complex may be critical to the stability of both the astral- and anastral-spindle pole.

Time-lapse analyses of normal cellular behaviours and signalling by fibroblast growth factor (FGF) provide new insights into the cell motions and molecules that form the posterior nervous system.

In the Drosophila egg, during signalling through the epidermal growth factor (EGF) receptor, a conformational switch, which is dependent on mitogen-activated protein kinase (MAPK) leads to the Cf2 transcriptio-nal repressor being targeted for proteolysis. Recent work shows that this switch is catalysed by the Drosophila homologue of Pin1, a peptidyl-prolyl isomerase.

The endosomal system includes distinct endocytic compartments where decisions are made that determine the destinations of extracellular and plasma membrane materials that have been internalized. A new family of proteins has been found that governs the exit of material from one of these endocytic organelles, the endosomal recycling compartment (ERC).

Expression of the cell cycle inhibitor p15^INK4b is suppressed by the Myc oncoprotein and induced by transforming growth factor-β (TGF-β). The transcription factor Miz-1 activates the Ink4b promoter, and interacts with Myc and TGF-β-activated Smad proteins. Miz-1 is thus a point of convergence for these antagonistic signals in cell-cycle control.

Caveolae deliver simian virus 40 (SV40) to a new compartment called a caveosome, where the virus is sorted for transport to the smooth endoplasmic reticulum (ER). This pathway bypasses other endocytic organelles, and early steps may be shared by lipid rafts and certain glycosylphosphatidylinositol (GPI)-linked proteins.

A crucial aspect of cell function in tissues is the biophysical interactions of the cell with the surrounding extracellular matrix. A fascinating report in this issue offers a major advance in the techniques available for investigating how the transmission of cell-generated forces to an underlying substratum is regulated. Application of this approach should provide key insights into such force regulation during cell migration and matrix contraction.