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NGF-Dependent neurite outgrowth in PC12 cells overexpressing the Src homology 2-domain protein shb requires activation of the Rap1 pathway.
Exp Cell Res. 2000 Sep 15; 259(2):370-7.EC

Abstract

The Src homology 2 (SH2) domain adaptor protein Shb has been shown to transmit NGF- and FGF-2-dependent differentiation signals in PC12 cells. To study if this involves signaling through the small GTPase Rap1, Rap1 activity was assessed in Shb-overexpressing PC12 cells. We demonstrate that NGF and EGF induce Rap1 activation in PC12-Shb cells, while FGF-2 fails to do so. However, PC12 cells expressing Shb with an inactivated SH2 domain do not respond to NGF stimulation with Rap1 activation. The CrkII SH2 domain interacts with Shb and a 130- to 135-kDa phosphotyrosine protein present mainly in PC12-Shb cells and these interactions may thus relate to the effect of Shb on Rap1 activation. Transient expression of RalGDS-RBD or Rap1GAP to block the Rap1 pathway reduces the NGF-dependent neurite outgrowth in PC12-Shb cells. These results suggest a role of Shb in NGF-dependent Rap1 signaling and this pathway may be of significance for neurite outgrowth under certain conditions.

Authors+Show Affiliations

Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10964504

Citation

Lu, L, et al. "NGF-Dependent Neurite Outgrowth in PC12 Cells Overexpressing the Src Homology 2-domain Protein Shb Requires Activation of the Rap1 Pathway." Experimental Cell Research, vol. 259, no. 2, 2000, pp. 370-7.
Lu L, Annerén C, Reedquist KA, et al. NGF-Dependent neurite outgrowth in PC12 cells overexpressing the Src homology 2-domain protein shb requires activation of the Rap1 pathway. Exp Cell Res. 2000;259(2):370-7.
Lu, L., Annerén, C., Reedquist, K. A., Bos, J. L., & Welsh, M. (2000). NGF-Dependent neurite outgrowth in PC12 cells overexpressing the Src homology 2-domain protein shb requires activation of the Rap1 pathway. Experimental Cell Research, 259(2), 370-7.
Lu L, et al. NGF-Dependent Neurite Outgrowth in PC12 Cells Overexpressing the Src Homology 2-domain Protein Shb Requires Activation of the Rap1 Pathway. Exp Cell Res. 2000 Sep 15;259(2):370-7. PubMed PMID: 10964504.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NGF-Dependent neurite outgrowth in PC12 cells overexpressing the Src homology 2-domain protein shb requires activation of the Rap1 pathway. AU - Lu,L, AU - Annerén,C, AU - Reedquist,K A, AU - Bos,J L, AU - Welsh,M, PY - 2000/8/31/pubmed PY - 2000/10/7/medline PY - 2000/8/31/entrez SP - 370 EP - 7 JF - Experimental cell research JO - Exp Cell Res VL - 259 IS - 2 N2 - The Src homology 2 (SH2) domain adaptor protein Shb has been shown to transmit NGF- and FGF-2-dependent differentiation signals in PC12 cells. To study if this involves signaling through the small GTPase Rap1, Rap1 activity was assessed in Shb-overexpressing PC12 cells. We demonstrate that NGF and EGF induce Rap1 activation in PC12-Shb cells, while FGF-2 fails to do so. However, PC12 cells expressing Shb with an inactivated SH2 domain do not respond to NGF stimulation with Rap1 activation. The CrkII SH2 domain interacts with Shb and a 130- to 135-kDa phosphotyrosine protein present mainly in PC12-Shb cells and these interactions may thus relate to the effect of Shb on Rap1 activation. Transient expression of RalGDS-RBD or Rap1GAP to block the Rap1 pathway reduces the NGF-dependent neurite outgrowth in PC12-Shb cells. These results suggest a role of Shb in NGF-dependent Rap1 signaling and this pathway may be of significance for neurite outgrowth under certain conditions. SN - 0014-4827 UR - https://www.unboundmedicine.com/medline/citation/10964504/NGF_Dependent_neurite_outgrowth_in_PC12_cells_overexpressing_the_Src_homology_2_domain_protein_shb_requires_activation_of_the_Rap1_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(00)94984-X DB - PRIME DP - Unbound Medicine ER -