Exploring the evolutionary history of MAP kinases in eukaryotes, this overview highlights their critical role in cellular signal transduction and the diversification seen in vertebrates. It delves into the functional specialization of MAPKs, including ERK, JNK, and p38 kinases, and their intricate substrate recognition mechanisms that ensure signaling precision. The text also examines the cooperation of binding sites and the importance of negative feedback in MAPK pathways.
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MAP Kinases are pivotal enzymes in eukaryotic signal transduction pathways
Bifurcation of Classical and Atypical MAP Kinases
The MAPK family is divided into classical and atypical kinases, with the former further subdivided into several groups
Presence of Classical MAPKs in Terrestrial Plants
Terrestrial plants possess four classical MAPK groups that are integral to their stress response mechanisms
Divergence of Classical MAPKs in Opisthokonts
In opisthokonts, classical MAPKs diverge into two principal branches: the ERK/Fus3-like kinases and the p38/Hog1-like kinases
Some MAP kinases exhibit ambiguous origins due to extensive divergence or their status as early derivatives of the MAPK lineage
The MAPK family has undergone significant expansion in vertebrates, partly due to two rounds of whole-genome duplication
Paralogs within Classical MAPK Groups
Vertebrates have multiple paralogs within each classical MAPK group, such as ERK1 and ERK2, and JNK1, JNK2, and JNK3
Paralogs within p38 Kinases
The p38 kinases in vertebrates also exhibit paralogous relationships, with p38 alpha and beta as one pair, and p38 gamma and delta as another
The ERK5 kinase, vital for vascular development in vertebrates, represents a specialized lineage that has disappeared in protostomes but is retained in cnidarians, sponges, and some unicellular relatives of multicellular animals
The classical and atypical MAP kinases diverged early in the history of eukaryotes, as evidenced by significant divergence among existing genes and the presence of atypical MAPKs in basal eukaryotes
The genome of Giardia lamblia encodes two MAPK genes, one similar to mammalian MAPKs and another similar to mammalian ERK7, while the multicellular amoeba Dictyostelium discoideum has both classical and atypical MAPKs
Atypical MAPKs are also present in higher plants, though their functions are less well-characterized due to a lack of research
MAP kinases, belonging to the CMGC kinase group, are distinguished by a consensus sequence for substrate recognition, typically a serine or threonine preceding a proline
Utilization of Auxiliary Regions for Substrate Identification
Unlike cyclin-dependent kinases, MAP kinases use auxiliary regions on their kinase domains for substrate identification
Importance of Hydrophobic Docking Groove and CD-Region for D-Motif Recognition
The hydrophobic docking groove and the negatively charged CD-region are crucial for recognizing D-motifs, which are important for the interaction and activation between MAP2Ks and MAPKs
MAP kinases possess additional substrate-binding sites, such as the DEF site, which is important for selectively binding to active MAP kinases
MAP kinases can establish negative feedback loops, such as the FxFP motif in the KSR1 scaffold protein, to modulate the intensity of their signaling pathways
00
______ are crucial enzymes in eukaryotic ______ pathways, affecting numerous cellular processes.
Mitogen-activated protein kinases (MAPKs)
signal transduction
01
Land plants have four classical MAPK groups, from ______ to ______, which are crucial for their ______ response mechanisms.
MAPK-A
MAPK-D
stress
02
Paralogs within kinase groups in vertebrates
Due to genome duplication, vertebrates have multiple paralogs in each kinase group, such as ERK1/ERK2.
