Arginine vasopressin stimulates mesangial cell proliferation by activating the epidermal growth factor receptor

Paramita M Ghosh, Margarita Mikhailova, Roble Bedolla, Jeffrey I. Kreisberg

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

The potent vasoconstrictor arginine vasopressin (AVP) is also a mitogen for mesangial cells. Treatment with AVP decreased transit time through the cell cycle. AVP-stimulated mesangial cell growth by activating both the Ras mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3-kinase (PI3K) cell signaling pathways. Both the selective PI3K inhibitor LY-294002 and the MAPK kinase (MEK) inhibitor PD-98059 inhibited AVP-stimulated mesangial cell proliferation. However, LY-294002 was more potent, indicating an important role for PI3K activation in AVP-stimulated mesangial cell proliferation. AVP appeared to exert its effect on MAPK and PI3K activation, as well as on cell proliferation, by activating the epidermal growth factor receptor (EGF-R). Pretreatment with the tyrphostin-derived EGF-R antagonist AG-1478 inhibited mesangial cell proliferation as well as the activation of extracellular signal-regulated kinase 1/2 (ERK1/2 or p42/ p44MAPK), and p70S6 kinase, a downstream effector of PI3K, providing evidence that MAPK and PI3K activation, respectively, occurred downstream of EGF-R activation. Treatment with rapamycin, an inhibitor of the p70S6 kinase activator mTOR, also resulted in growth inhibition, further suggesting the importance of the PI3K signaling pathway in AVP-induced proliferation. AVP treatment appeared to transactivate EGF-R by inducing tyrosine phosphorylation of the Ca2+/protein kinase C (PKC)-dependent nonreceptor tyrosine kinase, Pyk2, leading to Pyk2/c-Src association and c-Src activation. This was followed by association of c-Src with EGF-R and EGF-R activation. These data suggested that AVP-stimulated Pyk2 tyrosine phosphorylation to activate c-Src, thereby leading to EGF-R transactivation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume280
Issue number6 49-6
StatePublished - 2001
Externally publishedYes

Fingerprint

Mesangial Cells
Arginine Vasopressin
Phosphatidylinositol 3-Kinase
Epidermal Growth Factor Receptor
Cell Proliferation
Mitogen-Activated Protein Kinases
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Mitogen-Activated Protein Kinase Kinases
Tyrosine
Phosphotransferases
Phosphorylation
Tyrphostins
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Vasoconstrictor Agents
Sirolimus
Growth
Mitogens
Protein-Tyrosine Kinases
Protein Kinase C

Keywords

  • c-Src
  • Mitogen-activated protein kinase
  • P70S6 kinase
  • Phosphatidylinositol 3-kinase
  • Pyk2

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Arginine vasopressin stimulates mesangial cell proliferation by activating the epidermal growth factor receptor. / Ghosh, Paramita M; Mikhailova, Margarita; Bedolla, Roble; Kreisberg, Jeffrey I.

In: American Journal of Physiology - Renal Physiology, Vol. 280, No. 6 49-6, 2001.

Research output: Contribution to journalArticle

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