Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CAK1 encodes a protein kinase in Saccharomyces cerevisiae whose sole essential mitotic role is to activate the Cdc28p cyclin-dependent kinase by phosphorylation of threonine-169 in its activation loop. SMK1 encodes a sporulation-specific mitogen-activated protein (MAP) kinase homolog that is required to regulate the postmeiotic events of spore wall assembly. CAK1 was previously identified as a multicopy suppressor of a weakened smk1 mutant and shown to be required for spore wall assembly. Here we show that Smk1p, like other MAP kinases, is phosphorylated in its activation loop and that Smk1p is not activated in a cak1 missense mutant. Strains harboring a hyperactivated allele of CDC28 that is CAK1 independent and that lacks threonine-169 still require CAK1 to activate Smk1p. The data indicate that Cak1p functions upstream of Smk1p by activating a protein kinase other than Cdc28p. We also found that mutants lacking CAK1 are blocked early in meiotic development, as they show substantial delays in premeiotic DNA synthesis and defects in the expression of sporulation-specific genes, including IME1. The early meiotic role of Cak1p, like the postmeiotic role in the Smk1p pathway, is CDC28 independent. The data indicate that Cak1p activates multiple steps in meiotic development through multiple protein kinase targets.
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PMID:CAK1 promotes meiosis and spore formation in Saccharomyces cerevisiae in a CDC28-independent fashion. 1173 22

Sclerotial development is fundamental to the disease cycle of the omnivorous broad host range fungal phytopathogen Sclerotinia sclerotiorum. We have isolated a highly conserved homolog of ERK-type mitogen-activated protein kinases (MAPKs) from S. sclerotiorum (Smk1) and have demonstrated that Smk1 is required for sclerotial development. The smk1 transcription and MAPK enzyme activity are induced dramatically during sclerotiogenesis, especially during the production of sclerotial initials. When PD98059 (a specific inhibitor of the activation of MAPK by MAPK kinase) was applied to differentiating cultures or when antisense expression of smk1 was induced, sclerotial maturation was impaired. The smk1 transcript levels were highest under acidic pH conditions, suggesting that Smk1 regulates sclerotial development via a pH-dependent signaling pathway, involving the accumulation of oxalic acid, a previously identified pathogenicity factor that functions at least in part by reducing pH. Addition of cyclic AMP (cAMP) inhibited smk1 transcription, MAPK activation, and sclerotial development. Thus, S. sclerotiorum can coordinate environmental signals (such as pH) to trigger a signaling pathway mediated by Smk1 to induce sclerotia formation, and this pathway is negatively regulated by cAMP.
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PMID:MAPK regulation of sclerotial development in Sclerotinia sclerotiorum is linked with pH and cAMP sensing. 1507 73

Spore formation in Saccharomyces cerevisiae involves the sequential deposition of multiple spore wall layers between the prospore membranes that surround each meiotic product. The Smk1p mitogen-activated protein (MAP) kinase plays a critical role in spore formation, but the proteins that interact with Smk1p to regulate spore morphogenesis have not been described. Using mass spectrometry, we identify Gsc2p as a Smk1p-associated protein. Gsc2p is a 1,3-beta-glucan synthase subunit involved in synthesizing an inner spore wall layer. We find that 1,3-beta-glucan synthase activity is elevated in smk1 mutants, suggesting that SMK1 negatively regulates GSC2. Although deposition of the two inner spore wall layers is normal in smk1 mutants, deposition of the outer layers is aberrant. However, eliminating GSC2 activity restores normal deposition of the third spore wall layer in smk1 mutants, indicating that negative regulation of GSC2 by SMK1 is important for spore wall deposition. Our findings suggest a model for the coordination of spore wall layer deposition in which Smk1p facilitates the transition between early and late phases of spore wall deposition by inhibiting a spore wall-synthesizing enzyme important for early phases of spore wall deposition.
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PMID:The Smk1p MAP kinase negatively regulates Gsc2p, a 1,3-beta-glucan synthase, during spore wall morphogenesis in Saccharomyces cerevisiae. 1611 83