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Báo cáo Y học: Identification of syntaxin-1A sites of phosphorylation by casein kinase I and casein kinase II

Casein kinases I (CKI) are serine/threonine protein kinases widely expressed in a range of eukaryotes including yeast, mammals and plants. They have been shown to play a role in diverse physiological events including membrane trafficking. CKIa is associated with synaptic vesicles and phosphorylates some synaptic vesicle associated proteins including SV2. In this report, we show that syntaxin-1A is phosphorylated in vitro by CKI on Thr21. Casein kinase II (CKII) has been shown previously to phosphorylate syntaxin-1A in vitro and we have identified Ser14 as the CKII phosphorylation site, which is known to be phosphorylated in vivo | Eur. J. Biochem. 269 909-914 2002 FEBS 2002 Identification of syntaxin-IA sites of phosphorylation by casein kinase I and casein kinase II Thierry Dubois1 Preeti Kerai2 Michele Learmonth1 Andy Crenshaw1 and Alastair Aitken1 1The University of Edinburgh Division of Biomedical and Clinical Laboratory Sciences UK 2Division of Protein Structure National Institute for Medical Research London UK Casein kinases I CKI are serine threonine protein kinases widely expressed in a range of eukaryotes including yeast mammals and plants. They have been shown to play a role in diverse physiological events including membrane trafficking. CKIa is associated with synaptic vesicles and phosphorylates some synaptic vesicle associated proteins including SV2. In this report we show that syntaxin-lA is phosphorylated in vitro by CKI on Thr21. Casein kinase II CKII has been shown previously to phosphorylate syntaxin-1A in vitro and we have identified Ser14 as the CKII phosphorylation site which is known to be phosphorylated in vivo. As syntaxin-1A plays a key role in the regulation of neurotransmitter release by forming part of the SNARE soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex we propose that CKI may play a role in synaptic vesicle exocytosis. Keywords CKI CKII syntaxin-1A trafficking. Casein kinase I CKI belongs to a family of serine threonine protein kinases with seven isoforms identified in mammals CKI a b Ỗ e y1 y2 and y3 reviewed in 1 . The kinase domain is highly conserved between members of the CKI family but unique N- and C-terminal tails characterize each isoform. In yeast the functions of CKI have been much more extensively studied compared to their mammalian counterparts. Recently many reports have linked yeast CKIs to cytokinesis and vesicle trafficking especially in endocytosis 2-9 . Mammalian CKIs appear to have similar functions and also have been involved in DNA repair circadian rhythms and wnt signaling. Like their yeast counterparts .