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PAK1, PAK1Δ15, and PAK2: similarities, differences and mutual interactions

Dana Grebeňová1, Aleš Holoubek1, Pavla Röselová1

  • 1Department of Proteomics, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20, Prague, Czech Republic.

Scientific Reports
|November 22, 2019
PubMed

Insights

P21-activated kinases (PAK) exhibit complex interactions and non-redundant roles in cell adhesion and spreading. PAK1 isoforms and PAK2 show distinct localization and functional interplay, impacting cancer-related processes.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Cancer Research

Background:

  • P21-activated kinases (PAK) are crucial downstream effectors of small GTPases and Src family kinases.
  • PAK1 plays significant roles in cancer progression, including proliferation, adhesion, and migration.
  • Specific functions of PAK1 isoforms and functional overlap between PAK1 and PAK2 remain unclear.

Purpose of the Study:

  • To investigate the intracellular localization and interactions of PAK1 isoforms (PAK1-full, PAK1Δ15) and PAK2.
  • To elucidate the functional roles of different PAK members in cell adhesion and spreading.
  • To understand the interplay among PAK group I members.

Main Methods:

  • Utilized fluorescently tagged PAK1-full, PAK1Δ15, and PAK2 for localization and interaction studies.
  • Employed co-immunoprecipitation to detect direct interactions between PAK isoforms and PAK2.
  • Assessed cell-surface adhesion and spreading using real-time microimpedance measurements following PAK inhibition or depletion.

Main Results:

  • PAK1Δ15 and PAK2, unlike PAK1-full, localized to focal adhesions, suggesting C-terminal importance for localization.
  • Direct interactions were observed between PAK1 and PAK2, forming homodimers and heterocomplexes.
  • PAK1Δ15/PAK2 interaction correlated with cleavage, while PAK2 depletion impaired cell attachment and PAK1-full influenced cell spreading.

Conclusions:

  • PAK group I members (PAK1 isoforms and PAK2) exhibit complex interplay and possess non-redundant functions.
  • The C-terminus of PAK proteins influences their intracellular localization.
  • Distinct roles of PAK1-full and PAK2 in cell adhesion and spreading highlight their specific contributions to cellular processes.

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