PAK1 and aPKCzeta regulate myosin II-B phosphorylation: a novel signaling pathway regulating filament assembly.
Many signaling pathways regulate the function of the cellular cytoskeleton. Yet we know very little about the proteins involved in the cross-talk between the signaling and the cytoskeletal systems. Here we show that myosin II-B, an important cytoskeletal protein, resides in a complex with p21-activated kinase 1 (PAK1) and atypical protein kinase C (PKC) zeta (aPKCzeta) and that the interaction between these proteins is EGF-dependent. We further show that PAK1 is involved in aPKCzeta phosphorylation and that aPKCzeta phosphorylates myosin II-B directly on a specific serine residue in an EGF-dependent manner. This latter phosphorylation is specific to isoform B of myosin II, and it leads to slower filament assembly of myosin II-B. Furthermore, a decrease in aPKCzeta expression in the cells alters myosin II-B cellular organization. Our finding of a new signaling pathway involving PAK1, aPKCzeta, and myosin II-B, which is implicated in myosin II-B filament assembly and cellular organization, provides an important link between the signaling system and cytoskeletal dynamics.
Even-Faitelson
Liron
L
Department of Biochemistry, Institute of Medical Sciences, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
Ravid
Shoshana
S
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000595:Amino Acid Sequence; D003599:Cytoskeleton / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009154:Mutation; D024501:Nonmuscle Myosin Type IIB / Q000032:analysis / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000032:analysis / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D054462:p21-Activated Kinases; D000099221:Protein Kinase C zeta
D004815:Epidermal Growth Factor; D024501:Nonmuscle Myosin Type IIB; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D012694:Serine; D054462:p21-Activated Kinases; D000099221:Protein Kinase C zeta; C515903:PAK1 protein, human