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Oncogenic receptor tyrosine kinase signaling is driven by the Golgi protein GOLPH3 and its interaction with MYO18A

Kyle A Starost1, Jagadeeswara R Bommi1, Marshall C Peterman

  • 1Department of Medicine, Institute for Transformative Molecular Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.

Science Signaling
|May 19, 2026
PubMed

Insights

Golgi phosphoprotein 3 (GOLPH3) enhances receptor tyrosine kinase (RTK) delivery to the cell surface, driving cancer signaling. Targeting the GOLPH3-myosin 18A complex offers a new cancer therapy strategy.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Receptor tyrosine kinase (RTK) signaling is crucial in cancer development and is a key therapeutic target.
  • Golgi phosphoprotein 3 (GOLPH3) is an oncoprotein localized to the Golgi apparatus that influences signaling pathways, including mTOR.
  • Understanding RTK signaling modulators can reveal oncogenic mechanisms and identify novel therapeutic targets.

Purpose of the Study:

  • To investigate the role of GOLPH3 in RTK signaling pathways.
  • To elucidate the mechanism by which GOLPH3 influences RTK activity.
  • To explore the therapeutic potential of targeting GOLPH3 in cancer.

Main Methods:

  • Analysis of RTK signaling pathways in the presence of GOLPH3.
  • Investigating the interaction between GOLPH3 and its binding partner, myosin 18A (MYO18A).
  • Assessing the impact of the GOLPH3-MYO18A complex on RTK delivery to the plasma membrane.

Main Results:

  • GOLPH3 enhances the delivery of RTKs to the plasma membrane, thereby increasing downstream signaling.
  • This function is dependent on the interaction between GOLPH3 and MYO18A.
  • The GOLPH3-MYO18A complex at the Golgi is essential and rate-limiting for RTK signaling.

Conclusions:

  • GOLPH3 plays a critical role in regulating RTK signaling by controlling receptor delivery to the cell surface.
  • The GOLPH3-MYO18A complex is a key regulator of RTK signaling at the Golgi apparatus.
  • GOLPH3 represents a potential therapeutic target for cancers driven by RTK signaling.

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