Dynein light chain 1 phosphorylation controls macropinocytosis.
Recent studies have identified dynein light chain-1 (DLC1), a component of the dynein motor, as a p21-activated kinase 1 (Pak1)-interacting substrate with binding sites mapped to amino acids 61-89 of DLC1 and phosphorylation site at serine 88. Here we investigated the role of DLC1 phosphorylation by Pak1 upon the process of macropinocytosis. We found that Pak1 associates with dynein motor and that Pak1-DLC1 interaction starts at the initiation of pinosome formation and persists in early and late endosomes. Pak1 phosphorylation of DLC1 on Ser-88 controls vesicle formation and trafficking functions, as Ser-88 substitution for alanine prevents macropinocytosis. A peptide spanning the C-terminal 19-amino acid region of DLC1 efficiently blocked Ser-88 phosphorylation and macropinocytosis. These results suggest that the regulation of DLC1 by Pak1 is a novel mechanism by which a signaling kinase might influence macropinocytosis.
Yang
Zhibo
Z
Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Vadlamudi
Ratna K
RK
Kumar
Rakesh
R
D000818:Animals; D002460:Cell Line; D056445:Cytoplasmic Dyneins; D004398:Dyneins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D010873:Pinocytosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D054462:p21-Activated Kinases
C515903:PAK1 protein, human; C515905:Pak1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; C427758:DYNLL1 protein, human; C486041:Dync1li1 protein, mouse; D056445:Cytoplasmic Dyneins; D004398:Dyneins