Erratum: Multivalent cations depress ligand affinity of insulin-like growth factor-binding proteins-3 and -5 on human GM-10 fibroblast cell surfaces. J Cell Biochem 69:364–375.

Sackett RL, M^cCusker RH (1998): Multivalent cations depress ligand affinity of insulin-like growth factor-binding proteins-3 and -5 on human GM-10 fibroblast cell surfaces. J Cell Biochem 69:364–375.     

Initiation of cell locomotility is a morphogenetic checkpoint in thyroid epithelial cells regulated by ERK and PI3-kinase signals.

Epithelial locomotility is a fundamental determinant of tissue patterning that is subject to strict physiological regulation. The current study sought to identify cellular signals that initiate cell migration in cultured thyroid epithelial cells. Porcine thyroid cells cultured as 3-dimensional follicles convert to 2-dimensional monolayers when deprived of agents that stimulate cAMP/PKA signaling. This morphogenetic event is driven by the activation of cell-on-substrate locomotility, providing a convenient assay for events that regulate the initiation of locomotion. In this system, the extracellular signal regulated kinase (ERK) pathway became activated as follicles converted to monolayer, as demonstrated by immunoblotting for activation-specific phosphorylation and nuclear accumulation of ERK. Inhibition of ERK activation using the drug PD98059 effectively prevented cells from beginning to migrate. PD98059 inhibited cell spreading, actin filament reorganization and the assembly of focal adhesions, cellular events that mediate the initiation of thyroid cell locomotility. Akt (PKB) signaling was also activated during follicle-to-monolayer conversion and the phosphoinositide 3-kinase (PI3-kinase) inhibitor, wortmannin, also blocked the initiation of cell movement. Wortmannin did not, however, block activation of ERK signaling. These findings, therefore, identify the ERK and PI3-kinase signaling pathways as important stimulators of thyroid cell locomotility. These findings are incorporated into a model where the initiation of thyroid cell motility constitutes a morphogenetic checkpoint regulated by coordinated changes in stimulatory (ERK, PI3-kinase) and tonic inhibitory (cAMP/PKA) signaling pathways.     

Expression of M-N#1, a histo-blood group B-like antigen, is strongly up-regulated in nonapoptosing mammary epithelial cells during rat mammary gland involution.

Antibodies against the histo-blood group B-like antigen M-N#1 efficiently block the growth in vivo of rat mammary carcinoma cells that bear the antigen (Sleeman et al., 1999, Oncogene 18, 4485--4494). To try to understand the function of the M-N#1 antigen, we investigated when and where the antigen is expressed during the normal function of the rat mammary gland. Expression was virtually only seen during mammary gland involution. Here, strong expression of the antigen was observed in mammary epithelial cells, beginning around 2 days postweaning and lasting throughout the involution process. Dexamethasone treatment of animals postlactation inhibited alveolar collapse and remodeling in the mammary gland but inhibited neither the apoptosis of mammary epithelial cells nor the expression of the M-N#1 antigen. We show that up-regulation of carbohydrate antigens is not a general phenomenon during mammary gland involution, and thus that M-N#1 antigen expression is specifically regulated. Up-regulation of alpha(1,2)fucosyltransferase A, an enzyme required for M-N#1 antigen synthesis, is at least partly responsible for regulated M-N#1 antigen expression postlactation. Most significantly, we observed that the M-N#1 antigen is virtually exclusively expressed on nonapoptosing epithelial cells in the involuting mammary gland. These data suggest that M-N#1 antigen expression might either provide a survival function and/or be expressed in epithelial cells that are destined to grow and remodel mammary duct structures.     

JAM-L–mediated leukocyte adhesion to endothelial cells is regulated in cis by α4β1 integrin activation

Junctional adhesion molecules (JAMs) are endothelial and epithelial adhesion molecules involved in the recruitment of circulating leukocytes to inflammatory sites. We show here that JAM-L, a protein related to the JAM family, is restricted to leukocytes and promotes their adhesion to endothelial cells. Cis dimerization of JAM-L is required to engage in heterophilic interactions with its cognate counter-receptor CAR (coxsackie and adenovirus receptor). Interestingly, JAM-L expressed on neutrophils binds CAR independently of integrin activation. However, on resting monocytes and T lymphocytes, which express the integrin VLA-4, JAM-L molecules engage in complexes with VLA-4 and mainly accumulate in their monomeric form. Integrin activation is required for the dissociation of JAM-L–VLA-4 complexes and the accumulation of functional JAM-L dimers, which indicates that the leukocyte integrin VLA-4 controls JAM-L function in cis by controlling its dimerization state. This provides a mechanism through which VLA-4 and JAM-L functions are coordinately regulated, allowing JAM-L to strengthen integrin-dependent adhesion of leukocytes to endothelial cells.