Chimaerins, novel non-protein kinase C phorbol ester receptors, associate with Tmp21-I (p23): evidence for a novel anchoring mechanism involving the chimaerin C1 domain.
The regulation and function of chimaerins, a family of "non-protein kinase C" (PKC) phorbol ester/diacylglycerol receptors with Rac-GAP activity, is largely unknown. In a search for chimaerin-interacting proteins, we isolated Tmp21-I (p23), a protein localized at the perinuclear Golgi area. Remarkably, phorbol esters translocate beta2-chimaerin to the perinuclear region and promote its association with Tmp21-I in a PKC-independent manner. A deletional analysis revealed that the C1 domain in chimaerins is required for the interaction with Tmp21-I, thereby implying a novel function for this domain in protein-protein associations in addition to its role in lipid and phorbol ester binding. Our results support the emerging concept that multiple pathways transduce signaling by phorbol esters and revealed that, like PKC isozymes, chimaerins are subject to a positional regulation. In this setting, Tmp21-I serves as an anchoring protein that determines the intracellular localization of these novel phorbol ester receptors.
Wang
HongBin
H
Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160, USA.
Kazanietz
Marcelo G
MG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D019556:COS Cells; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D020740:Chimerin Proteins / Q000737:chemistry / Q000378:metabolism*; D017931:DNA Primers; D006160:Guanosine Triphosphate / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D020740:Chimerin Proteins; D017931:DNA Primers; D008565:Membrane Proteins; D011955:Receptors, Drug; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D006160:Guanosine Triphosphate; D011493:Protein Kinase C