The extracellular linker of pro-neuregulin-alpha2c is required for efficient sorting and juxtacrine function.

The neuregulins (NRGs) play important roles in animal physiology, and their disregulation has been linked to diseases such as cancer or schizophrenia. The NRGs may be produced as transmembrane proteins (proNRGs), even though they lack an N-terminal signal sequence. This raises the question of how NRGs are sorted to the plasma membrane.

Activation of ErbB2 by overexpression or by transmembrane neuregulin results in differential signaling and sensitivity to herceptin.

The ligands of the epidermal growth factor family and their receptors, the ErbB proteins, have been linked to the development of different types of cancer. Particular attention has focused on ErbB2, whose activation may occur by receptor overexpression or by ligand-induced oligomerization with other ErbB receptors. Whether these two modes of ErbB2 activation cause the same biological responses is unknown.

Overexpression of RasN17 fails to neutralize endogenous Ras in MCF7 breast cancer cells.

Receptor tyrosine kinases of the ErbB family have been implicated in the onset/progression of a number of neoplasias. In these diseases, ErbB receptor expression may be accompanied by constitutive activation caused by molecular alterations, overexpression, or ligand binding. An important signaling route activated by these receptors that has been linked to the stimulation of cell proliferation is the Ras route.

Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated shedding.

The ectodomain of certain transmembrane proteins can be released by the action of cell surface proteases, termed secretases. Here we have investigated how mitogen-activated protein kinases (MAPKs) control the shedding of membrane proteins. We show that extracellular signal-regulated kinase (Erk) acts as an intermediate in protein kinase C-regulated TrkA cleavage.

Mitogen-activated protein kinase-dependent and -independent routes control shedding of transmembrane growth factors through multiple secretases.

Solubilization of a number of membrane proteins occurs by the action of cell-surface proteases, termed secretases. Recently, the activity of these secretases has been reported to be controlled by the extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2) and the p38 mitogen-activated protein kinase (MAPK) routes. In the present paper, we show that shedding of membrane-anchored growth factors (MAGFs) may also occur through MAPK-independent routes.

Erk5 participates in neuregulin signal transduction and is constitutively active in breast cancer cells overexpressing ErbB2.

The four receptor tyrosine kinases of the ErbB family play essential roles in several physiological processes and have also been implicated in tumor generation and/or progression. Activation of ErbB1/EGFR is mainly triggered by epidermal growth factor (EGF) and other related ligands, while activation of ErbB2, ErbB3, and ErbB4 receptors occurs by binding to another set of EGF-like ligands termed neuregulins (NRGs). Here we show that the Erk5 mitogen-activated protein kinase (MAPK) pathway participates in NRG signal transduction.