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Requirement of Gαi1/3-Gab1 signaling complex for keratinocyte growth factor-induced PI3K-AKT-mTORC1 activation

Yi-Ming Zhang1, Zhi-Qing Zhang2, Yuan-Yuan Liu2

  • 1Department of Plastic and Cosmetic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

The Journal of Investigative Dermatology
|August 1, 2014
PubMed

Insights

G protein subunits (Gαi1/3) are crucial for keratinocyte growth factor signaling, mediating cell proliferation and migration. These findings highlight Gαi1/3

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Dermatology

Background:

  • Keratinocyte growth factor (KGF) signaling is vital for skin cell functions.
  • KGF receptor (KGFR) activation triggers downstream pathways like PI3K-AKT-mTORC1.
  • The precise upstream regulators of KGF-induced signaling remain incompletely understood.

Purpose of the Study:

  • To investigate the role of G protein α-subunits (Gαi1/3) and Gab1 in KGF-mediated signaling.
  • To elucidate the mechanism by which Gαi1/3 influences KGFR activation and downstream pathways.
  • To explore the potential involvement of Gαi1/3 in skin wound healing and keloid formation.

Main Methods:

  • Utilized cultured skin keratinocytes and KGF stimulation.
  • Employed short hairpin RNA (shRNA) to knockdown Gαi1/3 expression.
  • Analyzed protein complex formation, phosphorylation events, and cell signaling pathway activation (PI3K-AKT-mTORC1).
  • Assessed cell proliferation, migration, and expression of key proteins (cyclin D1, fibronectin).
  • Examined Gαi1/3 expression in wounded and keloid human skin tissues.

Main Results:

  • Gαi1/3 proteins form a complex with KGFR upon KGF stimulation.
  • Gαi1/3 is essential for Gab1 recruitment, phosphorylation, and subsequent PI3K-p85 activation.
  • Knockdown of Gαi1/3 significantly inhibits KGF-induced keratinocyte proliferation, migration, and cyclin D1/fibronectin accumulation.
  • Increased Gαi1/3 expression was observed in wounded and keloid skin tissues.

Conclusions:

  • Gαi1/3 proteins act downstream of KGFR but upstream of Gab1-mediated PI3K-AKT-mTORC1 pathway activation.
  • Gαi proteins play a critical role in mediating KGFR signaling, impacting cell migration.
  • Gαi1/3 may be involved in physiological processes such as wound healing and pathological conditions like keloid formation.

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