Src family kinases directly regulate JIP1 module dynamics and activation.
JIP1 is a mammalian scaffold protein that assembles and participates in regulating the dynamics and activation of components of the mixed-lineage kinase-dependent JNK module. Mechanisms governing JIP1-JNK module regulation remain unclear. JIP1 is a multiply phosphorylated protein; for this reason, it was hypothesized that signaling by unidentified protein kinases or phosphatases might determine module function. We find that Src family kinases directly bind and tyrosine phosphorylate JIP1 under basal conditions in several naturally occurring systems and, by doing so, appear to provide a regulated signal that increases the affinity of JIP1 for DLK and maintains the JIP-JNK module in a catalytically inactive state.
Nihalani
Deepak
D
University of Michigan Medical School, Medical Science Research Building 2, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0676, USA.
Wong
Hetty
H
Verma
Rakesh
R
Holzman
Lawrence B
LB
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000595:Amino Acid Sequence; D000596:Amino Acids; D000818:Animals; D002384:Catalysis; D002460:Cell Line; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics; D051381:Rats; D019061:src-Family Kinases / Q000378:metabolism / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; C490665:Mapk8ip protein, mouse; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; D020930:MAP Kinase Kinase Kinases; C090757:mitogen-activated protein kinase kinase kinase 12