CNK2 Couples NGF Signal Propagation to Multiple Regulatory Cascades Driving Cell Differentiation

• Published in: Current biology Vol. 14; no. 5; pp. 439 - 445
• Main Authors: Bumeister, Ron, Rosse, Carine, Anselmo, Anthony, Camonis, Jacques, White, Michael A
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 09.03.2004
• Subjects: Adaptor Proteins, Signal Transducing; Animals; Blotting, Western; Carrier Proteins - metabolism; Carrier Proteins - physiology; Cell Differentiation - physiology; DNA Primers; Enzyme Activation; Gene Expression - physiology; HeLa Cells; Humans; Immunohistochemistry; MAP Kinase Signaling System - physiology; Membrane Proteins - metabolism; Membrane Proteins - physiology; Microfilament Proteins; Mitogen-Activated Protein Kinases - metabolism; Mitogen-Activated Protein Kinases - physiology; Nerve Growth Factor - metabolism; Nerve Tissue Proteins - metabolism; Neurites - metabolism; PC12 Cells; Plasmids - genetics; Precipitin Tests; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2004.02.037

Neuronal precursor cells have the capacity to engage the Raf-MEK-ERK signal module to drive either of two distinctly different regulatory programs, proliferation and differentiation. This is, at least in part, a consequence of stimulus-specific shaping of the kinase cascade response. For example, the mitogen EGF induces a transient ERK activation, whereas the neurotrophin NGF induces prolonged ERK activation [1]. Here we define a novel component of the regulatory machinery contributing to the selective integration of MAP kinase signaling with discrete biological responses. We show that the scaffold/adaptor protein CNK2/MAGUIN-1 is required for NGF- but not EGF-induced ERK activation. In addition, CNK2 makes a separate, essential contribution to the coupling of NGF signaling to membrane/cytoskeletal remodeling. We propose that CNK2 integrates multiple regulatory pathways that must function in concert to drive an appropriate biological response to external stimuli.