{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPEAK3 is a newly identified member of the New Kinase Family 3 (NKF3), an evolutionarily conserved kinase‐like pseudokinase found across mammals and birds. Distinct from its family members that promote cell elongation, PEAK3 regulates cell motility without inducing an elongated cell shape; instead, its overexpression is associated with disruption and loss of actin filaments. This discovery establishes PEAK3 as a significant modulator of cytoskeletal dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "In addition, PEAK3 exerts its function by interacting with key regulators of cell motility. An unbiased search for binding partners identified the adaptor protein CrkII among others, and further experiments revealed that PEAK3 binds CrkII to prevent CrkII‐dependent membrane ruffling—a critical event in the remodeling of cell membranes during migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "Mechanistically, the regulatory role of PEAK3 depends on its ability to dimerize via a conserved split helical dimerization domain, a feature shared within the NKF3 family. Disruption of the conserved DFG motif within its pseudokinase domain impairs both its dimerization and its binding to CrkII, highlighting the importance of the pseudokinase domain’s conformation in its signaling function. These insights underscore a unique mechanism by which PEAK3 influences cell motility and potentially cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mitchell L Lopez, Megan Lo, Jennifer E Kung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PEAK3/C19orf35 pseudokinase, a new NFK3 kinase family member, inhibits CrkII through dimerization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1906360116"}], "href": "https://doi.org/10.1073/pnas.1906360116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31311869"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31311869"}]}]}]}