The Akt–mTORC1 pathway mediates Axl receptor tyrosine kinase-induced mesangial cell proliferation

Yuxuan Zhen, Tracy L. McGaha, Fred D. Finkelman, Wen Hai Shao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Glomerulonephritis (GN), an important pathologic feature of many renal diseases, is frequently characterized by mesangial cell proliferation. We and others have previously shown that the TAM family receptor tyrosine kinases Axl, Mer, and Tyro-3 contribute to cell survival, proliferation, migration, and clearance of apoptotic cells (ACs); that Axl contributes to GN by promoting mesangial cell proliferation; and that small molecule inhibition of Axl ameliorates nephrotoxic serum-induced GN in mice. We now show that stimulation of renal mesangial cell Axl causes a modest increase in intracellular Ca2+ and activates NF-κB, mTOR, and the mTOR-containing mTORC1 complex, which phosphorylates the ribosomal protein S6. Axl-induction of Akt activation is upstream of NF-κB and mTOR activation, which are mutually codependent. Axl-induced NF-κB activation leads to Bcl-xl up-regulation. Axl is more important than Mer at mediating AC phagocytosis by mesangial cells, but less important than Mer at mediating phagocytosis of ACs by peritoneal macrophages. Taken together, our data suggest the possibility that Axl mediates mesangial cell phagocytosis of ACs and promotes mesangial cell proliferation by activating NF-κB and mTORC1.

Original languageEnglish (US)
Pages (from-to)563-571
Number of pages9
JournalJournal of Leukocyte Biology
Issue number3
StatePublished - Mar 2022
Externally publishedYes


  • Axl
  • NF-κB
  • TAM receptors
  • apoptotic cell clearance
  • mTORC1
  • mesangial cell proliferation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology


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