Loovers Harriet M, Veenstra Kees, Snippe Helena, Pesesse Xavier, Erneux Christophe, van Haastert Peter J M
Department of Biochemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
J Biol Chem. 2003 Feb 21;278(8):5652-8. doi: 10.1074/jbc.M208396200. Epub 2002 Dec 2.
Inositol phosphate-containing molecules play an important role in a broad range of cellular processes. Inositol 5-phosphatases participate in the regulation of these signaling molecules. We have identified four inositol 5-phosphatases in Dictyostelium discoideum, Dd5P1-4, showing a high diversity in domain composition. Dd5P1 possesses only a inositol 5-phosphatase catalytic domain. An unique domain composition is present in Dd5P2 containing a RCC1-like domain. RCC1 has a seven-bladed propeller structure and interacts with G-proteins. Dd5P3 and Dd5P4 have a domain composition similar to human Synaptojanin with a SacI domain and OCRL with a RhoGAP domain, respectively. We have expressed the catalytic domains and show that these inositol 5-phosphatases have different substrate preferences. Single and double gene inactivation suggest a functional redundancy for Dd5P1, Dd5P2, and Dd5P3. Inactivation of the gene coding for Dd5P4 leads to defects in growth and development. These defects are restored by the expression of the complete protein but not by the 5-phosphatase catalytic domain.
含肌醇磷酸的分子在广泛的细胞过程中发挥着重要作用。肌醇5-磷酸酶参与这些信号分子的调节。我们在盘基网柄菌中鉴定出了四种肌醇5-磷酸酶，即Dd5P1 - 4，它们在结构域组成上具有高度多样性。Dd5P1仅拥有一个肌醇5-磷酸酶催化结构域。Dd5P2具有独特的结构域组成，包含一个类RCC1结构域。RCC1具有七叶螺旋桨结构，并与G蛋白相互作用。Dd5P3和Dd5P4的结构域组成分别类似于具有SacI结构域的人类突触素1和具有RhoGAP结构域的OCRL。我们表达了催化结构域，并表明这些肌醇5-磷酸酶具有不同的底物偏好。单基因和双基因失活表明Dd5P1、Dd5P2和Dd5P3存在功能冗余。编码Dd5P4的基因失活会导致生长和发育缺陷。这些缺陷可通过完整蛋白的表达得以恢复，但不能通过5-磷酸酶催化结构域的表达恢复。
