Differential phosphorylation of NG2 proteoglycan by ERK and PKCalpha helps balance cell proliferation and migration.
Two distinct Thr phosphorylation events within the cytoplasmic domain of the NG2 proteoglycan help regulate the cellular balance between proliferation and motility. Protein kinase Calpha mediates the phosphorylation of NG2 at Thr2256, resulting in enhanced cell motility. Extracellular signal-regulated kinase phosphorylates NG2 at Thr2314, stimulating cell proliferation. The effects of NG2 phosphorylation on proliferation and motility are dependent on beta1-integrin activation. Differential cell surface localization of the two distinctly phosphorylated forms of NG2 may be the mechanism by which the NG2-beta1-integrin interaction promotes proliferation in one case and motility in the other. NG2 phosphorylated at Thr2314 colocalizes with beta1-integrin on microprotrusions from the apical cell surface. In contrast, NG2 phosphorylated at Thr2256 colocalizes with beta1-integrin on lamellipodia at the leading edges of cells. Thus, phosphorylation and the resulting site of NG2-integrin localization may determine the specific downstream effects of integrin signaling.
Makagiansar
Irwan T
IT
Cancer Center, The Burnham Institute for Medical Research, La Jolla, CA 92037, USA. irwan.makagiansar@emdbiosciences.com
Williams
Scott
S
Mustelin
Tomas
T
Stallcup
William B
WB
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001254:Astrocytoma / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics; D005822:Genetic Vectors; D006801:Humans; D006825:Hybridomas / Q000166:cytology; D019012:Integrin beta1 / Q000378:metabolism; D008545:Melanoma / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D018076:DNA, Complementary; D019012:Integrin beta1; D020928:Mitogen-Activated Protein Kinases; D051571:Protein Kinase C-alpha; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; D013912:Threonine; D000099216:Chondroitin Sulfate Proteoglycan 4