Disease relevance of CMK1

• Extracts from cmk1 delta cells, which lacked detectable p55 using an antiserum raised against a Staphylococcus aureus protein A-CMK1 fusion protein, possessed significant residual Ca2+/CAM-dependent protein kinase activity [1].

High impact information on CMK1

• Calmodulin is also required for endocytosis in yeast and participates in Ca2+-dependent, stress-activated signaling pathways through its regulation of a protein phosphatase, calcineurin, and the protein kinases, Cmk1p and Cmk2p [2].
• The cloned gene (CMK1) encodes an open reading frame that is homologous to the sequences of vertebrate type II CaM kinases [1].
• Neither over-production (11-fold) nor complete elimination of the CMK1 gene product had any detectably deleterious effect on yeast cell growth [1].
• However, mutation of a predicted regulatory site (Thr-192) to aspartic acid resulted in hyperactivation of CMK1 activity in the presence of CaM and causes cell cycle arrest in vivo [3].
• Loss of Cmk1 Ca(2+)-calmodulin-dependent protein kinase in yeast results in constitutive weak organic acid resistance, associated with a post-transcriptional activation of the Pdr12 ATP-binding cassette transporter [4].

Biological context of CMK1

• Deletion of the CMK1 and CMK2 genes, which encode CaMK, decreases the LD50 of pheromone compared with that for a wild-type strain but again has no effect in a cmd1-6 strain [5].
• Deletion of CMK1 causes reduction of conidiation and complete lack of pathogenicity to the host plant [6].
• Furthermore, three melanin genes show no or slight expression in the cmk1 mutant when conidia fail to germinate, suggesting that CMK1 plays a role in gene expression required for appressorial melanization [6].
• The cmk1 cDNA encodes a 335-amino acid protein with significant homology to mammalian CaMK-I, including a conserved sequence for phosphorylation by CaM kinase kinase [3].
• The predicted amino acid sequences of the two CMK products exhibit highest similarity with mammalian calmodulin-dependent multifunctional protein kinase II (CaM kinase II): the similarity within the N-terminal catalytic domain is about 40%, whereas that within the rest of the sequence is 25% [7].

Anatomical context of CMK1

• These results suggest the presence of a CaM-dependent protein kinase cascade in yeast and indicate that cmk1 may be important in cell cycle progression, a process known to be dependent on CaM in eukaryotic cells [3].

Physical interactions of CMK1

• A truncation mutant of cmk1 (d320) failed to bind CaM, indicating that the CaM-binding domain is at the extreme C terminus of the protein [3].

Regulatory relationships of CMK1

• Antibody raised against a peptide fragment of the CMK1 protein cross-reacts with the CMK2 product [7].

Other interactions of CMK1

• Another gene may be substituted for function of the CMK1 and CMK2 kinase in vivo, since elimination of both kinase genes is not lethal [7].
• The CMK1 gene has been cloned by hybridization using an oligonucleotide probe synthesized on the basis of the peptide sequence of purified yeast CaM kinase (Londesborough, J. (1989) J. Gen. Microbiol. 135, 3373-3383) [7].
• These findings suggest that MAF1 is required for the early differentiation phase of appressorium formation, whereas CMK1 is involved in the maturation of appressoria [8].
• The C. lagenarium CMK1 gene, a homologue of the Saccharomyces cerevisiae FUS3/KSS1 mitogen-activated protein (MAP) kinase genes, was shown to regulate conidial germination, appressorium formation, and invasive growth [9].

Analytical, diagnostic and therapeutic context of CMK1

• Immunoblotting with this antibody indicated that the CMK1 and CMK2 products have apparent molecular masses of 56 and 50 kDa, respectively, in yeast cells [7].

References