Leishmanial protein kinases phosphorylate components of the complement system

Tomas Hermoso, Zvi Fishelson, Steven I. Becker, Koret Hirschberg, Charles L. Jaffe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


Externally oriented protein kinases are present on the plasma membrane of the human parasite, Leishmania. Since activation of complement plays an important role in the survival of these parasites, we examined the ability of protein kinases from Leishmania major to phosphorylate components of the human complement system. The leishmanial protein kinase-1 (LPK-1) isolated from promastigotes of L.major was able to phosphorylate purified human C3, C5 and C9. Only the α-chain of C3 and C5 was phosphorylated. The β-chain appeared not to be a substrate for this enzyme. C3b which is formed by proteolytic cleavage of C3 was not phosphorylated by LPK-1. Trypsin treatment of phosphorylated C3 (P-C3) resulted in the disappearance of P from the α-chain. This was correlated with the conversion of the C3 α-chain to the α′-chain of C3b, and the appearance of a 9 kDa 32P fragment comigrating with the C3a fragment of C3. P-C3 was more resistant to cleavage by trypsin than nonphosphorylated C3. LPK-1 phosphorylated purified C3a and two synthetic peptides, C3a21R and YA-C3a10R, derived from its COOH-terminal end, which contain the C3a binding site to leukocytes and platelets. LPK-1 did not phosphorylate C3a8R. Phosphoamino acid analysis of the synthetic peptides indicated that serine 71 of C3a was phosphorylated by LPK-1. Treatment of C3 with either methylamine or freeze-thaw C3 (H2O) prevented phosphorylation by the LPK-1 suggesting that substrate conformation may be involved in recognition by the leishmanial enzyme. Viable L.major promastigotes could phosphorylate both C3 and C3b implying that more than one protein kinase is probably present on the surface of these parasites. Extracellular protein phosphorylation may play a role in the interaction of the parasite with the host's immune system and in the survival of Leishmania.

Original languageEnglish
Pages (from-to)4061-4067
Number of pages7
JournalEMBO Journal
Issue number13
StatePublished - 1991
Externally publishedYes


  • Complement proteins
  • Ecto-protein kinases
  • Leishmania major


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