The phosphorylation of CapZ-interacting protein (CapZIP) by stress-activated protein kinases triggers its dissociation from CapZ

Claire E. Eyers, Helen McNeill, Axel Knebel, Nick Morrice, Simon J.C. Arthur, Ana Cuenda, Philip Cohen (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)


A protein expressed in immune cells and muscle was detected in muscle extracts as a substrate for several SAPKs (stress-activated protein kinases). It interacted specifically with the F-actin capping protein CapZ in splenocytes, and was therefore termed 'CapZIP' (CapZ-interacting protein). Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. Anisomycin induced the phosphorylation of CapZIP at Ser-179 in Jurkat cells, which was prevented by SB 203580, consistent with phosphorylation by MAPKAP-K2 and/or MAPKAP-K3. However, osmotic shock-induced phosphorylation of Ser-179 was unaffected by SB 203580. These and other results suggest that CapZIP is phosphorylated at Ser-179 in cells by MAPKAP-K2/MAPKAP-K3, and at least one other protein kinase. Stress-activated MAP kinase family members phosphorylated human CapZIP at many sites, including Ser-68, Ser-83, Ser-108 and Ser-216. Ser-108 became phosphorylated when Jurkat cells were exposed to osmotic shock, which was unaffected by SB 203580 and/or PD184352, or in splenocytes from mice that do not express either SAPK3/p38y or SAPK4/p385. Our results suggest that CapZIP may be phosphorylated by JNK (c-Jun N-terminal kinase), which phosphorylates CapZIP to > 5 mol/mol within minutes in vitro. Osmotic shock or anisomycin triggered the dissociation of CapZIP from CapZ in Jurkat cells, suggesting that phosphorylation of CapZIP may regulate the ability of CapZ to remodel actin filament assembly in vivo.

Original languageEnglish
Pages (from-to)127-135
Number of pages9
JournalBiochemical Journal
Issue number1
Publication statusPublished - 1 Jul 2005


  • Actin
  • c-Jun N-terminal kinase (JNK)
  • Cytoskeleton
  • Immune cell
  • Muscle
  • p38 mitogen-activated protein kinase (p38 MAPK)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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