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Class I PI 3-kinases: Function and evolution.

Nisha Kriplani1, Miguel A Hermida1, Euan R Brown1

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Class I phosphoinositide 3-kinases (PI3K) regulate cell growth and survival. Their evolutionary analysis reveals PI3K pathway components originated in single-celled organisms before metazoan co-option.

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Area of Science:

  • Cell Biology
  • Evolutionary Biology
  • Biochemistry

Background:

  • Class I phosphoinositide 3-kinases (PI3K) are crucial regulators of fundamental cellular processes in humans, including growth, proliferation, survival, and polarity.
  • Activation of PI3Ks by cell surface receptors generates the lipid second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3), which controls downstream signaling.
  • PIP3 directly modulates the function of numerous effector proteins, forming a complex signaling network.

Purpose of the Study:

  • To review the fundamental biology of the PI3K pathway.
  • To analyze the evolutionary distribution and origins of PI3K pathway components and their functions across different taxa.
  • To provide a phylogenetic framework for understanding human cellular process regulation.

Main Methods:

  • Literature review of PI3K pathway biology.
  • Phylogenetic analysis of PI3K pathway components, including class I PI3Ks, AKT, and Cytohesins.
  • Comparative genomics and functional analysis across metazoa, amoebozoa, and choanoflagellates.

Main Results:

  • Class I PI3Ks are broadly distributed across metazoa, amoebozoa, and choanoflagellates, indicating ancient origins in unicellular organisms.
  • The PI3K pathway likely evolved in single-celled organisms and was subsequently co-opted for intercellular communication in metazoans.
  • Downstream PIP3-binding proteins like AKT and Cytohesins show a similar ancient distribution, while other effectors evolved later.

Conclusions:

  • The PI3K pathway has deep evolutionary roots, originating before the emergence of multicellular animals.
  • Understanding the evolutionary history of the PI3K pathway provides insights into the conservation and divergence of cellular regulation mechanisms.
  • Genomic and functional phylogenies of regulatory systems like the PI3K pathway are essential for deciphering human cellular processes.