Export of secretory cargo from the ER occurs in vesicles bearing the COPII coat complex. Increasing evidence indicates that the process is regulated by phosphorylation. However, the protein kinases involved have remained unclear. Now, on , David Stephens and colleagues report that PCTAIREs - a branch of the cyclin-dependent kinase family - interact directly with COPII and modulate cargo transport. To identify regulators of COPII function, they used two-hybrid screening with the human COPII subunit Sec23 as bait. One positive clone encoded a fragment of PCTAIRE-3, one of three PCTAIRE isoforms. The authors then used co-immunoprecipitation studies in cell lysates to show that recombinant PCTAIRE-1 and PCTAIRE-3 can both interact with Sec23. Finally, they demonstrate that specifically inhibiting PCTAIRE kinase activity causes gross changes in the organization and function of the early secretory pathway. Stephens and colleagues therefore conclude that PCTAIRE plays a role in this pathway by regulating COPII function.
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