The phosphorylation state of threonine-220, a uniquely phosphatase-sensitive protein kinase A site in microtubule-associated protein MAP2c, regulates microtubule binding and stability.
Phosphorylation of microtubule-associated protein 2 (MAP2) has a profound effect on microtubule stability and organization. In this work a consensus protein kinase A (PKA) phosphorylation site, T(220), of juvenile MAP2c is characterized. As confirmed by mass spectrometry, this site can be phosphorylated by PKA but shows less than average reactivity among the 3.5 +/- 0.5 phosphate residues incorporated into the protein. In contrast, T(220) is uniquely sensitive to dephosphorylation: three major Ser/Thr protein phosphatases, in the order of efficiency PP2B > PP2A(c) > PP1(c), remove this phosphate group first. MAP2c specifically dephosphorylated at this site binds and stabilizes microtubules stronger than either fully phosphorylated or nonphosphorylated MAP2c. Phosphorylation of this site also affects proteolytic sensitivity of MAP2c, which might represent a further level of control in this system. Thus, the phosphorylation state of T(220) may be a primary determinant of microtubule function.
D000595:Amino Acid Sequence; D000818:Animals; D002154:Calpain / Q000737:chemistry; D002417:Cattle; D016384:Consensus Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D010450:Endopeptidases / Q000737:chemistry; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D008870:Microtubules / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D013552:Swine; D013912:Threonine / Q000737:chemistry / Q000378:metabolism*
C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D013912:Threonine; D017868:Cyclic AMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D010450:Endopeptidases; D002154:Calpain; C449002:mu-calpain