PMID- 17947375 OWN - NLM STAT- MEDLINE DCOM- 20080709 LR - 20211020 IS - 0888-8809 (Print) IS - 1944-9917 (Electronic) IS - 0888-8809 (Linking) VI - 22 IP - 2 DP - 2008 Feb TI - SH2B1beta (SH2-Bbeta) enhances expression of a subset of nerve growth factor-regulated genes important for neuronal differentiation including genes encoding urokinase plasminogen activator receptor and matrix metalloproteinase 3/10. PG - 454-76 AB - Previous work showed that the adapter protein SH2B adapter protein 1beta (SH2B1) (SH2-B) binds to the activated form of the nerve growth factor (NGF) receptor TrkA and is critical for both NGF-dependent neurite outgrowth and maintenance. To identify SH2B1beta-regulated genes critical for neurite outgrowth, we performed microarray analysis of control PC12 cells and PC12 cells stably overexpressing SH2B1beta (PC12-SH2B1beta) or the dominant-negative SH2B1beta(R555E) [PC12-SH2B1beta(R555E)]. NGF-induced microarray expression of Plaur and Mmp10 genes was greatly enhanced in PC12-SH2B1beta cells, whereas NGF-induced Plaur and Mmp3 expression was substantially depressed in PC12-SH2B1beta(R555E) cells. Plaur, Mmp3, and Mmp10 are among the 12 genes most highly up-regulated after 6 h of NGF. Their protein products [urokinase plasminogen activator receptor (uPAR), matrix metalloproteinase 3 (MMP3), and MMP10] lie in the same pathway of extracellular matrix degradation; uPAR has been shown previously to be critical for NGF-induced neurite outgrowth. Quantitative real-time PCR analysis revealed SH2B1beta enhancement of NGF induction of all three genes and the suppression of NGF induction of all three when endogenous SH2B1 was reduced using short hairpin RNA against SH2B1 and in PC12-SH2B1beta(R555E) cells. NGF-induced levels of uPAR and MMP3/10 and neurite outgrowth through Matrigel (MMP3-dependent) were also increased in PC12-SH2B1beta cells. These results suggest that SH2B1beta stimulates NGF-induced neuronal differentiation at least in part by enhancing expression of a specific subset of NGF-sensitive genes, including Plaur, Mmp3, and/or Mmp10, required for neurite outgrowth. FAU - Chen, Linyi AU - Chen L AD - Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, MI 48109-0622, USA. FAU - Maures, Travis J AU - Maures TJ FAU - Jin, Hui AU - Jin H FAU - Huo, Jeffrey S AU - Huo JS FAU - Rabbani, Shafaat A AU - Rabbani SA FAU - Schwartz, Jessica AU - Schwartz J FAU - Carter-Su, Christin AU - Carter-Su C LA - eng SI - GEO/GSE4557 GR - R01 DK054222/DK/NIDDK NIH HHS/United States GR - T32 DK071212/DK/NIDDK NIH HHS/United States GR - 5P60 DK 20572/DK/NIDDK NIH HHS/United States GR - P60 DK020572/DK/NIDDK NIH HHS/United States GR - R01 DK 54222/DK/NIDDK NIH HHS/United States GR - T32 GM 07315/GM/NIGMS NIH HHS/United States GR - T32 DK 071212/DK/NIDDK NIH HHS/United States GR - T32 GM007315/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20071018 PL - United States TA - Mol Endocrinol JT - Molecular endocrinology (Baltimore, Md.) JID - 8801431 RN - 0 (Carrier Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Nerve Growth Factors) RN - 0 (Plaur protein, rat) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Urokinase Plasminogen Activator) RN - 0 (SH2B1 protein, rat) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.24.22 (Matrix Metalloproteinase 10) SB - IM MH - Animals MH - Carrier Proteins/*genetics/metabolism/physiology MH - Cell Differentiation/*drug effects/genetics MH - Gene Expression Regulation, Neoplastic/drug effects MH - Gene Silencing MH - Immunoblotting MH - Intracellular Signaling Peptides and Proteins MH - Matrix Metalloproteinase 10/*genetics/metabolism MH - Matrix Metalloproteinase 3/*genetics/metabolism MH - Models, Biological MH - Nerve Growth Factors/*pharmacology MH - Neurites/drug effects/metabolism MH - Neurons/cytology/drug effects/metabolism MH - Oligonucleotide Array Sequence Analysis MH - PC12 Cells MH - Rats MH - Receptors, Cell Surface/*genetics/metabolism MH - Receptors, Urokinase Plasminogen Activator MH - Reverse Transcriptase Polymerase Chain Reaction PMC - PMC2234583 EDAT- 2007/10/20 09:00 MHDA- 2008/07/10 09:00 PMCR- 2009/02/01 CRDT- 2007/10/20 09:00 PHST- 2007/10/20 09:00 [pubmed] PHST- 2008/07/10 09:00 [medline] PHST- 2007/10/20 09:00 [entrez] PHST- 2009/02/01 00:00 [pmc-release] AID - me.2007-0384 [pii] AID - 4185 [pii] AID - 10.1210/me.2007-0384 [doi] PST - ppublish SO - Mol Endocrinol. 2008 Feb;22(2):454-76. doi: 10.1210/me.2007-0384. Epub 2007 Oct 18.