Suppressor of cytokine signalling-2 and epidermal growth factor regulate neurite outgrowth of cortical neurons.
Factors that regulate neurite outgrowth are important in determining the wiring of the central nervous system. Here we describe that the intracellular regulator of cytokine signalling, suppressor of cytokine signalling-2 (SOCS2) and epidermal growth factor (EGF), both of which are expressed in the cortical plate during neural development, promote neurite outgrowth of cortical neurons. Cortical neurons derived from transgenic mice that over-express SOCS2 had an increased rate of neurite outgrowth and an increased length and number of primary neurites compared with wild-type neurons. EGF produced a similar effect in wild-type cortical neurons and further enhanced the SOCS2-induced neurite outgrowth. The mechanism of neurite outgrowth induction by SOCS2 and EGF at least partially overlapped as phosphorylation of the EGF receptor in SOCS2 over-expressing or EGF-stimulated neurons was increased on Tyrosine845, the Src binding site and neurite outgrowth in both protocols was blocked by inhibitors of the EGF receptor kinase and Src kinase.
Goldshmit
Yona
Y
Neural Regeneration Laboratory, Centre for Neuroscience, The University of Melbourne, Parkville, Victoria 3010, Australia.
Greenhalgh
Christopher J
CJ
Turnley
Ann M
AM
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000187:drug effects / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D016501:Neurites / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D012097:Repressor Proteins / Q000187:drug effects / Q000378:metabolism*; D018874:Spheroids, Cellular; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D012097:Repressor Proteins; C491409:Socs2 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D019061:src-Family Kinases