Cargando…

Spatial and temporal aspects and the interplay of Grb14 and protein tyrosine phosphatase-1B on the insulin receptor phosphorylation

BACKGROUND: Growth factor receptor-bound protein 14 (Grb14) is an adapter protein implicated in receptor tyrosine kinase signaling. Grb14 knockout studies highlight both the positive and negative roles of Grb14 in receptor tyrosine kinase signaling, in a tissue specific manner. Retinal cells are pos...

Descripción completa

Detalles Bibliográficos
Autores principales: Rajala, Raju VS, Basavarajappa, Devaraj K, Dighe, Radhika, Rajala, Ammaji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878334/
https://www.ncbi.nlm.nih.gov/pubmed/24350791
http://dx.doi.org/10.1186/1478-811X-11-96
_version_ 1782297784016175104
author Rajala, Raju VS
Basavarajappa, Devaraj K
Dighe, Radhika
Rajala, Ammaji
author_facet Rajala, Raju VS
Basavarajappa, Devaraj K
Dighe, Radhika
Rajala, Ammaji
author_sort Rajala, Raju VS
collection PubMed
description BACKGROUND: Growth factor receptor-bound protein 14 (Grb14) is an adapter protein implicated in receptor tyrosine kinase signaling. Grb14 knockout studies highlight both the positive and negative roles of Grb14 in receptor tyrosine kinase signaling, in a tissue specific manner. Retinal cells are post-mitotic tissue, and insulin receptor (IR) activation is essential for retinal neuron survival. Retinal cells express protein tyrosine phosphatase-1B (PTP1B), which dephosphorylates IR and Grb14, a pseudosubstrate inhibitor of IR. This project asks the following major question: in retinal neurons, how does the IR overcome inactivation by PTP1B and Grb14? RESULTS: Our previous studies suggest that ablation of Grb14 results in decreased IR activation, due to increased PTP1B activity. Our research propounds that phosphorylation in the BPS region of Grb14 inhibits PTP1B activity, thereby promoting IR activation. We propose a model in which phosphorylation of the BPS region of Grb14 is the key element in promoting IR activation, and failure to undergo phosphorylation on Grb14 leads to both PTP1B and Grb14 exerting their negative roles in IR. Consistent with this hypothesis, we found decreased phosphorylation of Grb14 in diabetic type 1 Ins2(Akita) mouse retinas. Decreased retinal IR activation has previously been reported in this mouse line. CONCLUSIONS: Our results suggest that phosphorylation status of the BPS region of Grb14 determines the positive or negative role it will play in IR signaling.
format Online
Article
Text
id pubmed-3878334
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-38783342014-01-03 Spatial and temporal aspects and the interplay of Grb14 and protein tyrosine phosphatase-1B on the insulin receptor phosphorylation Rajala, Raju VS Basavarajappa, Devaraj K Dighe, Radhika Rajala, Ammaji Cell Commun Signal Research BACKGROUND: Growth factor receptor-bound protein 14 (Grb14) is an adapter protein implicated in receptor tyrosine kinase signaling. Grb14 knockout studies highlight both the positive and negative roles of Grb14 in receptor tyrosine kinase signaling, in a tissue specific manner. Retinal cells are post-mitotic tissue, and insulin receptor (IR) activation is essential for retinal neuron survival. Retinal cells express protein tyrosine phosphatase-1B (PTP1B), which dephosphorylates IR and Grb14, a pseudosubstrate inhibitor of IR. This project asks the following major question: in retinal neurons, how does the IR overcome inactivation by PTP1B and Grb14? RESULTS: Our previous studies suggest that ablation of Grb14 results in decreased IR activation, due to increased PTP1B activity. Our research propounds that phosphorylation in the BPS region of Grb14 inhibits PTP1B activity, thereby promoting IR activation. We propose a model in which phosphorylation of the BPS region of Grb14 is the key element in promoting IR activation, and failure to undergo phosphorylation on Grb14 leads to both PTP1B and Grb14 exerting their negative roles in IR. Consistent with this hypothesis, we found decreased phosphorylation of Grb14 in diabetic type 1 Ins2(Akita) mouse retinas. Decreased retinal IR activation has previously been reported in this mouse line. CONCLUSIONS: Our results suggest that phosphorylation status of the BPS region of Grb14 determines the positive or negative role it will play in IR signaling. BioMed Central 2013-12-18 /pmc/articles/PMC3878334/ /pubmed/24350791 http://dx.doi.org/10.1186/1478-811X-11-96 Text en Copyright © 2013 Rajala et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Rajala, Raju VS
Basavarajappa, Devaraj K
Dighe, Radhika
Rajala, Ammaji
Spatial and temporal aspects and the interplay of Grb14 and protein tyrosine phosphatase-1B on the insulin receptor phosphorylation
title Spatial and temporal aspects and the interplay of Grb14 and protein tyrosine phosphatase-1B on the insulin receptor phosphorylation
title_full Spatial and temporal aspects and the interplay of Grb14 and protein tyrosine phosphatase-1B on the insulin receptor phosphorylation
title_fullStr Spatial and temporal aspects and the interplay of Grb14 and protein tyrosine phosphatase-1B on the insulin receptor phosphorylation
title_full_unstemmed Spatial and temporal aspects and the interplay of Grb14 and protein tyrosine phosphatase-1B on the insulin receptor phosphorylation
title_short Spatial and temporal aspects and the interplay of Grb14 and protein tyrosine phosphatase-1B on the insulin receptor phosphorylation
title_sort spatial and temporal aspects and the interplay of grb14 and protein tyrosine phosphatase-1b on the insulin receptor phosphorylation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878334/
https://www.ncbi.nlm.nih.gov/pubmed/24350791
http://dx.doi.org/10.1186/1478-811X-11-96
work_keys_str_mv AT rajalarajuvs spatialandtemporalaspectsandtheinterplayofgrb14andproteintyrosinephosphatase1bontheinsulinreceptorphosphorylation
AT basavarajappadevarajk spatialandtemporalaspectsandtheinterplayofgrb14andproteintyrosinephosphatase1bontheinsulinreceptorphosphorylation
AT digheradhika spatialandtemporalaspectsandtheinterplayofgrb14andproteintyrosinephosphatase1bontheinsulinreceptorphosphorylation
AT rajalaammaji spatialandtemporalaspectsandtheinterplayofgrb14andproteintyrosinephosphatase1bontheinsulinreceptorphosphorylation