CNK2 couples NGF signal propagation to multiple regulatory cascades driving cell differentiation.
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. 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.
Bumeister
Ron
R
Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9039, USA.
Rosse
Carine
C
Anselmo
Anthony
A
Camonis
Jacques
J
White
Michael A
MA
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers; D004789:Enzyme Activation; D015870:Gene Expression / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D008840:Microfilament Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology; D020932:Nerve Growth Factor / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism; D016716:PC12 Cells; D010957:Plasmids / Q000235:genetics; D011233:Precipitin Tests; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C479421:CNKSR2 protein, human; D002352:Carrier Proteins; C118898:Cnksr2 protein, rat; D017931:DNA Primers; C116887:EPB41L3 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D020932:Nerve Growth Factor; D020928:Mitogen-Activated Protein Kinases