Biology Reference
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do not translocate in the gb-null cell line in vivo or in vitro (S. Funamoto and
R. A. Firtel, unpublished observations). These observations suggest that the
translocation is dependent on the Gb subunit, possibly by directly binding to
PI3K or an associated protein, as reported for PI3Kg in mammalian cells.
However, it is unlikely that binding to Gb is responsible for the steep gradient
of membrane localization of PI3K, as the anterior-posterior gradient of Gb is
relatively shallow. Moreover, fluorescence resonance energy transfer (FRET)
technology revealed that G protein subunits remain disassociated as long as
receptors are occupied, which removes the possibility of asymmetric
localization of activated G proteins (Janetopoulos et al., 2001). We are
presently missing the polarized signal upstream of PI3K/PTEN.
References
Bokemeyer, D., Sorokin, A. and Du, M., 1996. Multiple intracelluar MAP kinase signaling
cascades. Kidney Int. 49: 1187-1198.
Buschmann, T., Fuchs, S., Lee, C., Pan, Z. and Ronai, Z., 2000. SUMO-1 modification of
Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53.
Cell 101: 753-762.
Chung, C. Y., Funamoto, S. and Firtel, R. A., 2001a. Signaling pathways controlling cell
polarity and chemotaxis. Trends Biochem. Sci. 26: 557-566.
Chung, C. Y., Potikyan, G. and Firtel, R. A., 2001b. Control of cell polarity and
chemotaxis by Akt/PKB and PI3 kinase through the regulation of PAKa. Mol. Cell 7:
937-947.
Comer, F. I. and Parent, C. A., 2002. PI 2-kinases and PTEN: How opposites
chemoattract. Cell 109: 541-544.
Devreotes, P. N. and Zigmond, S. H., 1988. Chemotaxis in eukaryotic cells: a focus on
leukocytes and Dictyostelium. Annu. Rev. Cell Biol. 4: 649-686.
Dowler, S., Currie, R. A., Downes, C. P. and Alessi, D. R., 1999. DAPP1: a dual adaptor
for phosphotyrosine and 3-phosphoinositides. Biochem. J. 342: 7-12.
Dowler, S., Currie, R. A., Campbell, D. G., Deak, M., et al., 2000. Identification of
pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding
specificities. Biochem. J. 351: 19-31.
Escobedo, J. A., Navankasattusas, S., Kavanaugh, W. M., Milfay, D., et al., 1991. cDNA
cloning of a novel 85 kd protein that has SH2 domains and regulates binding of PI3-
kinase to the PDGF beta-receptor. Cell 65: 75-82.
Firtel, R. A. and Chung, C. Y., 2000. The molecular genetics of chemotaxis: sensing and
responding to chemoattractant gradients. BioEssays 22: 603-615.
Funamoto, S., Milan, K., Meili, R. and Firtel, R. A., 2001. Role of phosphatidylinositol 3'
kinase and a downstream pleckstrin homology domain-containing protein in controlling
chemotaxis in Dictyostelium. J. Cell Biol. 153: 795-810.
Funamoto, S., Meili, R., Lee, S., Parry. L. and Firtel, R. A., 2002. Spatial and temporal
regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis. Cell
109: 611-623.
