Nerve Growth Factor Receptor TrkA, a New Receptor in Insulin Signaling Pathway in PC12 Cells

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2013 Jun 11

PMID 23749991

Citations 15

Authors

Thangiah Geetha

Shraddha D Rege

Salome E Mathews

Susan O Meakin

Morris F White

Jeganathan Ramesh Babu

Affiliations

Soon will be listed here.

Abstract

TrkA is a cell surface transmembrane receptor tyrosine kinase for nerve growth factor (NGF). TrkA has an NPXY motif and kinase regulatory loop similar to insulin receptor (INSR) suggesting that NGF→TrkA signaling might overlap with insulin→INSR signaling. During insulin or NGF stimulation TrkA, insulin receptor substrate-1 (IRS-1), INSR (and presumably other proteins) forms a complex in PC12 cells. In PC12 cells, tyrosine phosphorylation of INSR and IRS-1 is dependent upon the functional TrkA kinase domain. Moreover, expression of TrkA kinase-inactive mutant blocked the activation of Akt and Erk5 in response to insulin or NGF. Based on these data, we propose that TrkA participates in insulin signaling pathway in PC12 cells.

Citing Articles

Nerve growth factor promotes differentiation and protects the oligodendrocyte precursor cells from hypoxia/ischemia.

Baldassarro V, Cescatti M, Rocco M, Aloe L, Lorenzini L, Giardino L Front Neurosci. 2023; 17:1111170.

PMID: 36875668 PMC: 9978228. DOI: 10.3389/fnins.2023.1111170.

Insulin action at a molecular level - 100 years of progress.

White M, Kahn C Mol Metab. 2021; 52:101304.

PMID: 34274528 PMC: 8551477. DOI: 10.1016/j.molmet.2021.101304.

Metabolic homeostasis via BDNF and its receptors.

Podyma B, Parekh K, Guler A, Deppmann C Trends Endocrinol Metab. 2021; 32(7):488-499.

PMID: 33958275 PMC: 8192464. DOI: 10.1016/j.tem.2021.04.005.

PC12 Cell Line: Cell Types, Coating of Culture Vessels, Differentiation and Other Culture Conditions.

Wiatrak B, Kubis-Kubiak A, Piwowar A, Barg E Cells. 2020; 9(4).

PMID: 32295099 PMC: 7227003. DOI: 10.3390/cells9040958.

Modulation of Sensory Nerve Function by Insulin: Possible Relevance to Pain, Inflammation and Axon Growth.

Lazar B, Jancso G, Santha P Int J Mol Sci. 2020; 21(7).

PMID: 32260335 PMC: 7177741. DOI: 10.3390/ijms21072507.

References

Hoyer S, Henneberg N, Knapp S, Lannert H, Martin E . Brain glucose metabolism is controlled by amplification and desensitization of the neuronal insulin receptor. Ann N Y Acad Sci. 1996; 777:374-9. DOI: 10.1111/j.1749-6632.1996.tb34448.x. View

Chao M . Trophic factors: An evolutionary cul-de-sac or door into higher neuronal function?. J Neurosci Res. 2000; 59(3):353-5. View

Virkamaki A, Ueki K, Kahn C . Protein-protein interaction in insulin signaling and the molecular mechanisms of insulin resistance. J Clin Invest. 1999; 103(7):931-43. PMC: 408269. DOI: 10.1172/JCI6609. View

Lemmon M, Schlessinger J . Cell signaling by receptor tyrosine kinases. Cell. 2010; 141(7):1117-34. PMC: 2914105. DOI: 10.1016/j.cell.2010.06.011. View

Kaplan D, Miller F . Signal transduction by the neurotrophin receptors. Curr Opin Cell Biol. 1997; 9(2):213-21. DOI: 10.1016/s0955-0674(97)80065-8. View

Geetha T, Jiang J, Wooten M . Lysine 63 polyubiquitination of the nerve growth factor receptor TrkA directs internalization and signaling. Mol Cell. 2005; 20(2):301-12. DOI: 10.1016/j.molcel.2005.09.014. View

Barbacid M, Lamballe F, Pulido D, Klein R . The trk family of tyrosine protein kinase receptors. Biochim Biophys Acta. 1991; 1072(2-3):115-27. DOI: 10.1016/0304-419x(91)90010-i. View

Wickelgren I . Tracking insulin to the mind. Science. 1998; 280(5363):517-9. DOI: 10.1126/science.280.5363.517. View

Geetha T, Wooten M . TrkA receptor endolysosomal degradation is both ubiquitin and proteasome dependent. Traffic. 2008; 9(7):1146-56. DOI: 10.1111/j.1600-0854.2008.00751.x. View

10.

Berg M, Sternberg D, Parada L, Chao M . K-252a inhibits nerve growth factor-induced trk proto-oncogene tyrosine phosphorylation and kinase activity. J Biol Chem. 1992; 267(1):13-6. View

11.

ONeill T, Craparo A, Gustafson T . Characterization of an interaction between insulin receptor substrate 1 and the insulin receptor by using the two-hybrid system. Mol Cell Biol. 1994; 14(10):6433-42. PMC: 359173. DOI: 10.1128/mcb.14.10.6433-6442.1994. View

12.

Uemura E, Greenlee H . Amyloid beta-peptide inhibits neuronal glucose uptake by preventing exocytosis. Exp Neurol. 2001; 170(2):270-6. DOI: 10.1006/exnr.2001.7719. View

13.

Chen D, Van Horn D, White M, Backer J . Insulin receptor substrate 1 rescues insulin action in CHO cells expressing mutant insulin receptors that lack a juxtamembrane NPXY motif. Mol Cell Biol. 1995; 15(9):4711-7. PMC: 230714. DOI: 10.1128/MCB.15.9.4711. View

14.

Craft S, Wiethop B, Murphy C, Nevins R, Fleischman S, Rice V . Effects of hyperglycemia on memory and hormone levels in dementia of the Alzheimer type: a longitudinal study. Behav Neurosci. 1993; 107(6):926-40. DOI: 10.1037//0735-7044.107.6.926. View

15.

Greenlee M, Uemura E, Carpenter S, Doyle R, Buss J . Glucose uptake in PC12 cells: GLUT3 vesicle trafficking and fusion as revealed with a novel GLUT3-GFP fusion protein. J Neurosci Res. 2003; 73(4):518-25. DOI: 10.1002/jnr.10684. View

16.

Levi-Montalcini R . The nerve growth factor 35 years later. Science. 1987; 237(4819):1154-62. DOI: 10.1126/science.3306916. View

17.

Riccio A, Pierchala B, Ciarallo C, Ginty D . An NGF-TrkA-mediated retrograde signal to transcription factor CREB in sympathetic neurons. Science. 1997; 277(5329):1097-100. DOI: 10.1126/science.277.5329.1097. View

18.

Friedman W, Greene L . Neurotrophin signaling via Trks and p75. Exp Cell Res. 1999; 253(1):131-42. DOI: 10.1006/excr.1999.4705. View

19.

Lee J, Pilch P, Shoelson S, Scarlata S . Conformational changes of the insulin receptor upon insulin binding and activation as monitored by fluorescence spectroscopy. Biochemistry. 1997; 36(9):2701-8. DOI: 10.1021/bi961815g. View

20.

Meakin S, Macdonald J, Gryz E, Kubu C, Verdi J . The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation. J Biol Chem. 1999; 274(14):9861-70. DOI: 10.1074/jbc.274.14.9861. View