JNK-interacting leucine zipper protein is a novel scaffolding protein in the Galpha13 signaling pathway.
Scaffolding proteins play a critical role in conferring specificity and fidelity to signaling pathways. The JNK-interacting leucine zipper protein (JLP) has been identified as a scaffolding protein involved in linking components of the JNK signaling module. Galpha(12) and Galpha(13), the alpha-subunits of heterotrimeric G proteins G12 and G13, respectively, stimulate the JNK module in diverse cell types. Here, we report that Galpha(13) physically interacts with JLP, and this interaction enhances Galpha(13)-mediated JNK activation. We also demonstrate endogenous interaction between JLP and Galpha(13) in MCF-7 cells. JLP interaction is specific to the G12 family of alpha-subunits via its C-terminal domain (termed GID-JLP), spanning amino acids 1165-1307, and this interaction is more pronounced with the mutationally or functionally activated form of Galpha(13) compared to that of wild-type Galpha(13). The presence of a ternary complex consisting of Galpha(13), JLP, and JNK suggests a role for JLP in tethering Galpha(13) to the signaling components involved in JNK activation. Coexpression of GID-JLP disrupts ternary complex formation in addition to attenuating Galpha(13)-stimulated JNK activity. These findings identify JLP as a novel scaffolding protein in the Galpha(13)-mediated JNK signaling pathway.
Kashef
Kimia
K
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Lee
Clement M
CM
Ha
Ji Hee
JH
Reddy
E Premkumar
EP
Dhanasekaran
Danny N
DN
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016350:Leucine Zippers; D009154:Mutation; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology*
D004268:DNA-Binding Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D044365:GTP-Binding Protein alpha Subunits, G12-G13