Ettinger S L, Lauener R W, Duronio V
Department of Medicine, Jack Bell Research Centre, University of British Columbia, Vancouver, British Columbia V6H 3Z6, Canada.
J Biol Chem. 1996 Jun 14;271(24):14514-8. doi: 10.1074/jbc.271.24.14514.
Phosphatidylinositol (PI) 3-kinase is activated as a result of cytokine-induced association of the enzyme with specific tyrosine-phosphorylated proteins. PI 3-kinase lipid products, PI 3, 4-P2 and PI 3,4,5-P3, have been shown, in vitro, to directly activate novel and atypical protein kinase C (PKC) isozymes. However, the mechanism by which PI 3-kinase may be involved in regulation of PKC isoforms in vivo is presently unknown. We investigated a possible relationship by looking for associations between these enzymes. We found that in a human erythroleukemia cell line, as well as in rabbit platelets, PI 3-kinase and PKCdelta associate in a specific manner that is modulated by cell activation. Granulocyte-macrophage colony-stimulating factor treatment of cells caused increased association of PKCdelta and PI 3-kinase as did treatment of platelets with platelet-activating factor. Results using two PI 3-kinase inhibitors, wortmannin and LY-294002, showed that the former inhibited this association, while the latter did not, suggesting that PI 3-kinase lipid products may not be a prerequisite for the PI 3-kinase/PKCdelta association. Our results also suggest that tyrosine phosphorylation of PKCdelta is not involved in its association with PI 3-kinase.
细胞因子诱导磷脂酰肌醇（PI）3激酶与特定酪氨酸磷酸化蛋白结合，从而激活该酶。PI 3激酶的脂质产物PI 3,4 - P2和PI 3,4,5 - P3在体外已被证明可直接激活新型和非典型蛋白激酶C（PKC）同工酶。然而，PI 3激酶在体内参与PKC同工型调节的机制目前尚不清楚。我们通过寻找这些酶之间的关联来研究一种可能的关系。我们发现，在人红白血病细胞系以及兔血小板中，PI 3激酶和PKCδ以一种受细胞激活调节的特定方式结合。用粒细胞巨噬细胞集落刺激因子处理细胞以及用血小板激活因子处理血小板均导致PKCδ与PI 3激酶的结合增加。使用两种PI 3激酶抑制剂渥曼青霉素和LY - 294002的结果表明，前者抑制这种结合，而后者则不然，这表明PI 3激酶的脂质产物可能不是PI 3激酶/PKCδ结合的必要条件。我们的结果还表明，PKCδ的酪氨酸磷酸化不参与其与PI 3激酶的结合。
