Journal of neuroscience research
-
N-cadherin and beta1-integrin adhesion and signaling play important roles in growth cone adhesion and guidance. Each of these adhesion receptor systems is composed of multiprotein complexes, and both adhesion and downstream signaling events are regulated through the interaction of protein tyrosine kinases and phosphatases with many of the proteins that make up these complex systems. Work from our laboratory reported that the nonreceptor protein tyrosine phosphatase PTP1B is localized to adherens junctions and focal adhesion complexes and regulates both N-cadherin- and beta1-integrin-mediated adhesion. ⋯ Moreover, suppressing the level of PTP1B in primary embryonic chick neural retina cells using antisense oligonucleotides also inhibits N-cadherin- and beta1-integrin-mediated neurite outgrowth. Neither of these techniques reduces the levels of expression of either adhesion receptor. We conclude that PTP1B is a regulatory component of the molecular complex required for both N-cadherin and beta1-integrin-mediated axon growth.
-
The common neurotrophin receptor p75(NTR) (low affinity nerve growth factor receptor) participates in the high-affinity binding with the TrkA nerve growth factor (NGF) receptor, may mediate apoptosis, and may signal independently in a cell-specific manner. The potential of p75(NTR) to signal independently of TrkA was investigated with an NGF mutant protein (NGFdelta9/13) that binds poorly to TrkA (Woo et al. [1995] J. Biol. ⋯ Finally, upon serum withdrawal, both NGF and the NGFdelta9/13 mutant activate nuclear translocation of the transcriptional factor NF-kappaB (nuclear factor kappaB), a process involved in cell survival. These results are consistent with p75(NTR) inhibition of caspase-mediated apoptosis in PC12 cells. The different physiologic responses elicited by NGFdelta9/13 indicate the potential for individual signaling by the two NGF receptors and also demonstrate the utility of NGF mutants for receptor-selective signal transduction.