Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis

Abstract

The cdc2+ protein kinase (pp34) is found to be phosphorylated on tyrosine as well as serine and threonine residues in exponentially growing Schizosaccharomyces pombe. At mitosis, the level of pp34 phosphorylation on both threonine and tyrosine residues decreases. The single detectable site of tyrosine phosphorylation in pp34 has been mapped to Tyr 15, a residue within the presumptive ATP-binding domain. Substitution of this tyrosine by phenylalanine advances cells prematurely into mitosis, establishing that tyrosine phosphorylation/dephosphorylation directly regulates pp34 function.

Mid1/anillin and the spatial regulation of cytokinesis in fission yeast

“…The role of Cdr2 as a mitotic inducer and the presence of the cell cycle regulatory kinases Cdr1 and Wee1 at medial cortical nodes has led to the hypothesis that during interphase, medial cortical nodes transduce the spatial information generated by Pom1 gradient to the cell cycle machinery [Martin and Berthelot-Grosjean, 2009;Moseley et al, 2009]: Wee1 phosphorylates the cyclin-dependent kinase Cdc2 to inhibit precocious mitotic entry [Gould and Nurse, 1989]; the SAD1-like kinases Cdr1/ Nim1 and Cdr2 [Coleman et al, 1993; Parker et al, 1993;Wu and Russell, 1993;Breeding et al, 1998;Kanoh and Russell, 1998] promote mitotic entry by inhibiting Wee1; Pom1, upstream of SAD1-kinases, has been shown to negatively regulate Cdr2 [Martin and Berthelot-Grosjean, 2009;Moseley et al, 2009]. These negative regulatory relationships together with the specific localization of Pom1 and Cdr2 within the cell lead to an elegant model explaining the coupling between mitosis entry and cell length.…”

Triggering the all-or-nothing switch into mitosis

“…During G2, the cyclin:Cdk1 of S. pombe, Drosophila, vertebrates, echinoderms and plants is held inactive by inhibitory phosphorylation of residues Y15 and T14 of Cdk1 [12][13][14][15][16][17] . Maintenance of this inhibitory phosphorylation is required for G2 quiescence [18][19][20] .…”

“…Reciprocally, loss of function of Cdc25, the phosphatase that removes the inhibitory phosphate, arrests cells in G2, and its overexpression drives G2 cells into mitosis 23 . Finally, expression of a mutant form of Cdk1 that is immune to inhibitory phosphorylation bypasses the need for Cdc25 and causes cells to escape G2 prematurely 12 . With the exception of S. cerevisiae, which lacks a G2 phase (Box 2), similar experiments in a variety of organisms have had a similar outcome, confirming that inhibitory phosphorylation of cyclin:Cdk1 is required for G2 and that the dephosphorylation of Cdk1 drives mitosis.…”

Substrate specificities of catalytic fragments of protein tyrosine phosphatases (HPTPβ, LAR, and CD45) toward phosphotyrosylpeptide substrates and thiophosphotyrosylated peptides as inhibitors

“…100-fold differential affinity of the PTPO catalytic domain for the pY 11-mer peptides from the (White et al, 1985;Tornqvist et al, 1987;Murakami & Rosen, 1991); EGFR, 1,167-1,177 of EGF receptor; lck394, 390-398 of ~5 6 ' '~ (Marth et al, 1988); lck505, 501-509 of p561Ck (Marth et al, 1988); src527, 523-531 of p60c-src (Cooper et al, 1986); PDGFRP-I, 748-755 of PDGF receptor chain (Kazlauskas & Cooper, 1989); PDGFRP-2, 746-756 of PDGF receptor chain; PLCy, 766-776 of phospholipase Cy (Kim et al, 1990); cdc2, 10-19 of ~3 4~~~' (Could & Nurse, 1989); {"TCR, 148-157 of T-cell receptor complex {chain (E. Reinherz, pers. comm.…”