D2A sequence of the urokinase receptor induces cell growth through αvβ3 integrin and EGFR

The urokinase receptor (uPAR) stimulates cell proliferation by forming a macromolecular complex with \u3b1v\u3b23 integrin and the epidermal growth factor receptor (EGFR, ErbB1 or HER1) that we name the uPAR proliferasome. uPAR transactivates EGFR, which in turn mediates uPAR-initiated mitogenic signal to the cell. EGFR activation and EGFR-dependent cell growth are blocked in the absence of uPAR expression or when uPAR activity is inhibited by antibodies against either uPAR or EGFR. The mitogenic sequence of uPAR corresponds to the D2A motif present in domain 2. NMR analysis revealed that D2A synthetic peptide has a particular three-dimensional structure, which is atypical for short peptides. D2A peptide is as effective as EGF in promoting EGFR phosphorylation and cell proliferation that were inhibited by AG1478, a specific inhibitor of the tyrosine kinase activity of EGFR. Both D2A and EGF failed to induce proliferation of NR6-EGFR-K721A cells expressing a kinase-defective mutant of EGFR. Moreover, D2A peptide and EGF phosphorylate ERK demonstrating the involvement of the MAP kinase signalling pathway. Altogether, this study reveals the importance of sequence D2A of uPAR, and the interdependence of uPAR and EGFR

CEP120 and SPICE1 cooperate with CPAP in centriole elongation

Centrosomes organize microtubule (MT) arrays and are comprised of centrioles surrounded by ordered pericentriolar proteins. Centrioles are barrel-shaped structures composed of MTs, and as basal bodies they template the formation of cilia/flagella. Defects in centriole assembly can lead to ciliopathies and genome instability. The assembly of procentrioles requires a set of conserved proteins. It is initiated at the G1-to-S transition by PLK4 and CEP152, which help recruit SASS6 and STIL to the vicinity of the mother centriole to organize the cartwheel. Subsequently, CPAP promotes centriolar MT assembly and elongation in G2. While centriole integrity is maintained by CEP135 and POC1 through MT stabilization, centriole elongation requires POC5 and is restricted by CP110 and CEP97. How strict control of centriole length is achieved remains unclear. Here, we show that CEP120 and SPICE1 are required to localize CEP135 (but not SASS6, STIL, or CPAP) to procentrioles. CEP120 associates with SPICE1 and CPAP, and depletion of any of these proteins results in short procentrioles. Furthermore, CEP120 or CPAP overexpression results in excessive centriole elongation, a process dependent on CEP120, SPICE1, and CPAP. Our findings identify a shared function for these proteins in centriole length control

The γTuRC Revisited: A Comparative Analysis of Interphase and Mitotic Human γTuRC Redefines the Set of Core Components and Identifies the Novel Subunit GCP8

We compared the composition of γ-tubulin ring complexes tandem-affinity purified from asynchronous and mitotic human cells by mass spectrometry. We identified various interactors including the novel core subunit GCP8. GCP8 is the first subunit with an interphase-specific role in centrosomal γ-tubulin recruitment and microtubule nucleation