A major in vivo substrate of Ca(2+)-phospholipid-dependent protein kinase (MARCKS) shows phosphorylation-dependent translocation between the cytoplasmic and the membrane fractions. The mechanism of the translocation was studied with purified MARCKS and various membranes. MARCKS was found to bind to pure phospholipid membranes as well as to the synaptic vesicle membranes. Although the interactio...

The dynamic rearrangement of the actin cytoskeleton is fundamental to most biological processes including embryogenesis, morphogenesis, cell movement, wound healing and metastasis [1]. Membrane ruffling and reversible cell-substratum interactions underlie actin-driven cell movement. Protein kinase C (PKC) stimulates membrane ruffling and adhesion [2], but the mechanism by which this occurs is u...

To understand how muscle cell spreading and survival are mediated by integrins, we studied the signaling events initiated by the attachment of muscle cells to fibronectin (FN). We have previously demonstrated that muscle cell spreading on FN is mediated by alpha5beta1 integrin, is associated with rapid phosphorylation of focal adhesion kinase and is dependent on activation of protein kinase C (...

m. MARCKS is a ubiquitous protein kinase C substrate which interacts with cahncdulh~ and cross-links the actin filaments Its cellular function is probably related to the regulation of these two proteins. MARCKS is also a physiological substrate for prolio&irected kinase.s like cyclindependent kinasea (cdks) and MAP kinases. The expression of MARCKS is high in quiescent fibroblasts. with a raoid...

m. MARCKS is a ubiquitous protein kinase C substrate which interacts with cahncdulh~ and cross-links the actin filaments Its cellular function is probably related to the regulation of these two proteins. MARCKS is also a physiological substrate for prolio&irected kinase.s like cyclindependent kinasea (cdks) and MAP kinases. The expression of MARCKS is high in quiescent fibroblasts. with a raoid...

PSMB5 mutations and upregulation of the β5 subunit of the proteasome represent key determinants of acquired resistance to the proteasome inhibitor bortezomib (BTZ) in leukemic cells in vitro. We here undertook a multi-modality (DNA, mRNA, miRNA) array-based analysis of human CCRF-CEM leukemia cells and BTZ-resistant subclones to determine whether or not complementary mechanisms contribute to BT...

Cell motility necessitates the rapid formation and disassembly of cell adhesions. We have studied adhesions in a highly motile melanoma cell line using various biochemical approaches and microscopic techniques to image close adhesions. We report that WM-1617 melanoma cells contain at least two types of close adhesion: classic focal adhesions and more extensive, irregularly shaped adhesions that...

MARCKS is a specific protein kinase C (PKC) substrate that binds both calmodulin and actin and is phosphorylated during phagocyte activation, neurosecretion, and growth factor-dependent mitogenesis. We report here on MacMARCKS, a MARCKS homolog, whose synthesis is dramatically increased in macrophages when these cells are exposed to bacterial lipopolysaccharide. We have purified rabbit MacMARCK...

Impairment of endothelial barrier function is implicated in many vascular and inflammatory disorders. One prevalent mechanism of endothelial dysfunction is an increase in reactive oxygen species under oxidative stress. Previous reports have demonstrated that hydrogen peroxide (H(2)O(2)), a highly stable reactive oxygen species that modulates physiological signaling pathways, also enhances endot...

Membrane binding of the myristoylated alanine-rich C kinase substrate (MARCKS) requires both its myristate chain and basic "effector" region. Previous studies with a peptide corresponding to the effector region, MARCKS-(151-175), showed that the 13 basic residues interact electrostatically with acidic lipids and that the 5 hydrophobic phenylalanine residues penetrate the polar head group region...