biostudies-literatureChang TWNational Health Research Institute, TaiwanNational Taiwan UniversityNational Health Research InstitutesMinistry of Education in TaiwanMinistry of Science and Technology in Taiwanjcs263812https://www.ebi.ac.uk/biostudies/studies/S-EPMC12148019biostudies-literatureUnknown138(10)Activation of extracellular signal-regulated kinases 1 and 2 (Erk1/2; also known as MAPK3 and MAPK1, respectively) at the plasma membrane usually leads to their translocation to various intracellular sites, where scaffolding proteins mediate substrate targeting. However, in platelet-derived growth factor (PDGF)-induced signaling, Erk1/2 phosphorylate Pak1 to drive cell migration while remaining at the plasma membrane, raising the question of whether scaffolding proteins are required. Similarly, the small GTPase Arf-like protein 4D (Arl4D) promotes cell migration by recruiting Pak1 to the plasma membrane and facilitating its phosphorylation, although the mechanism linking recruitment to phosphorylation remains unclear. To address these questions, we show that Arl4D functions as a scaffoldinJournal of cell scienceThe phosphorylation of Pak1 by Erk1/2 to drive cell migration requires Arl4D acting as a scaffolding protein.PMC12148019NSTC112-2320-B-002-019-MY3NHRI-EX113-11306BIYu CJChang TWLee FSLin MCfalseThe phosphorylation of Pak1 by Erk1/2 to drive cell migration requires Arl4D acting as a scaffolding protein.Activation of extracellular signal-regulated kinases 1 and 2 (Erk1/2; also known as MAPK3 and MAPK1, respectively) at the plasma membrane usually leads to their translocation to various intracellular sites, where scaffolding proteins mediate substrate targeting. However, in platelet-derived growth factor (PDGF)-induced signaling, Erk1/2 phosphorylate Pak1 to drive cell migration while remaining at the plasma membrane, raising the question of whether scaffolding proteins are required. Similarly, the small GTPase Arf-like protein 4D (Arl4D) promotes cell migration by recruiting Pak1 to the plasma membrane and facilitating its phosphorylation, although the mechanism linking recruitment to phosphorylation remains unclear. To address these questions, we show that Arl4D functions as a scaffoldin2025-01-01T00:00:00Z2025 May2026-06-03T06:03:46.22Z2026-05-29T03:05:51.804ZS-EPMC121480194030992510.1242/jcs.263812