title: AXL and MET crosstalk to promote gonadotropin releasing hormone (GnRH) neuronal cell migration and survival.
abstract: The membrane tyrosine kinase receptors, AXL and MET, are implicated in GnRH neuron migration and/or survival. We hypothesized that the receptors with their ligands, GAS6 and HGF, respectively may cross-talk in GnRH neuronal function. In NLT GnRH neuronal cells, MET co-immunoprecipitated with AXL, although HGF or GAS6 did not transphosphorylate AXL or MET, respectively. Co-expression of a kinase dead AXL blocked HGF activation of MET and indirectly AKT and p38MAPK. Silencing of AXL decreased HGF's ability to phosphorylate MET and activate AXL's downstream effectors, p38MAPK and AKT. HGF/MET signaling modulated neuron migration dependent and independent of AXL co-expression and p38MAPK. Conversely, AXL's control of GnRH neuronal survival was dependent on HGF/MET signaling. Together, these data support that the importance of membrane tyrosine kinase receptor crosstalk to regulate neuronal cell-specific developmental functions.
authors: Department of Medicine, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, CO 80045, USA.
authors: Smita
authors: S
authors: Salian-Mehta
authors: Mei
authors: M
authors: Xu
authors: Margaret E
authors: ME
authors: Wierman
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D002470:Cell Survival; D018507:Gene Expression Regulation, Developmental; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020239:Receptor Cross-Talk; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D007987:Gonadotropin-Releasing Hormone; D017228:Hepatocyte Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D019859:Proto-Oncogene Proteins c-met; D034741:RNA, Small Interfering; D020794:Receptor Protein-Tyrosine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C066855:HGF protein, human; C491743:MET protein, human
references: Am J Pathol. 1993 Sep;143(3):949-58
references: 8362987
references: Onkologie. 2009 Jun;32(6):331-6
references: 19521120
references: Cancer Res. 2007 Apr 15;67(8):3878-87
references: 17440102
references: Trends Endocrinol Metab. 2004 Apr;15(3):96-102
references: 15046737
references: Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3402-6
references: 2014260
references: Mol Cell Endocrinol. 2011 Jun 6;339(1-2):151-8
references: 21539887
references: J Neurooncol. 2010 Aug;99(1):33-40
references: 20157762
references: J Biol Chem. 1991 Nov 25;266(33):22087-90
references: 1718989
references: Cancer Metastasis Rev. 2008 Mar;27(1):85-94
references: 18175071
references: J Biol Chem. 2002 Oct 11;277(41):38133-40
references: 12138087
references: Cancer Lett. 2012 Jun 1;319(1):109-17
references: 22261330
references: Eur J Pharmacol. 2006 Mar 27;535(1-3):114-24
references: 16516191
references: Nature. 1995 Feb 23;373(6516):699-702
references: 7854452
references: Oncogene. 2000 Jun 22;19(27):3041-9
references: 10871856
references: Br J Cancer. 2011 Jul 26;105(3):407-12
references: 21730976
references: Nature. 1995 Aug 31;376(6543):768-71
references: 7651534
references: J Neuroendocrinol. 2010 Jul;22(7):743-53
references: 20646175
references: Endocrinology. 2002 Sep;143(9):3306-15
references: 12193542
references: Science. 1991 Feb 15;251(4995):802-4
references: 1846706
references: J Cell Biol. 1994 Jul;126(2):485-94
references: 8034747
references: Nature. 1998 Jan 15;391(6664):285-8
references: 9440692
references: Mol Biol Cell. 2005 Feb;16(2):550-61
references: 15548598
references: Neuron. 1990 Jul;5(1):1-10
references: 2196069
references: Nature. 1995 Feb 23;373(6516):702-5
references: 7854453
references: Nat Cell Biol. 2001 Jul;3(7):E161-2
references: 11433311
references: Mol Endocrinol. 1999 Feb;13(2):191-201
references: 9973250
references: J Invest Dermatol. 2012 Apr;132(4):1230-8
references: 22189792
references: Endocrinology. 2007 Jun;148(6):2806-14
references: 17332061
references: Oncogene. 1991 Apr;6(4):501-4
references: 1827664
references: J Biol Chem. 2000 Mar 24;275(12):8806-11
references: 10722725
references: Oncogene. 2000 Nov 20;19(49):5582-9
references: 11114738
references: Mol Endocrinol. 2008 Nov;22(11):2481-95
references: 18787040
references: BMC Cancer. 2011 May 19;11:180
references: 21595927
references: Front Neuroendocrinol. 2011 Jan;32(1):43-52
references: 20650288
references: Mol Cell Biol. 2002 Jan;22(2):599-613
references: 11756555
references: Nat Rev Mol Cell Biol. 2003 Dec;4(12):915-25
references: 14685170
references: J Oral Pathol Med. 2012 Aug;41(7):547-58
references: 22413835
references: J Neurosci. 2007 Jan 10;27(2):431-45
references: 17215404
references: Nat Rev Drug Discov. 2008 Jun;7(6):504-16
references: 18511928
references: J Biol Chem. 2006 Feb 24;281(8):4771-8
references: 16361255
references: Mol Cell Biol. 1995 Feb;15(2):614-25
references: 7823930
references: Nature. 1989 Mar 9;338(6211):161-4
references: 2645530
references: J Cell Biol. 2008 Nov 3;183(3):555-66
references: 18981235