LIG_MAPK_1
ELM server details
ELM
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Functional site class:
MAPK docking motif
Functional site description:
The docking interaction in the MAP kinase cascades is achieved through specific conserved regions on MAPKs (docking groove) and MAPK-interacting molecules (the MAPK docking motif). The docking motif is usually - but not always - the sequence of a substrate protein.
ELM(s): LIG_MAPK_1, LIG_MAPK_2
LIG_MAPK_1 description: MAPK interacting molecules (e.g. MAPKKs, substrates, phosphatases) carry docking motifs that help to regulate specific interactions in the MAPK cascade. The classic MAPK docking site was first identified in c-JUN, a substrate of JNK (Kallunki et al., 1996). This motif is characterized by a cluster of basic residues positioned upstream to a #-x-# motif. The substrates that carry this motif recognize a broad range of MAPKs (Sharrocks at al., 2000).
Pattern: [KR]{0,2}[KR].{0,2}[KR].{2,4}[ILVM].[ILVF]
Present in taxon(s): Eukaryota  
Not represented in taxon(s):

o See instances for LIG_MAPK_1


o Abstract

MAPK (Mitogen-activated protein kinase) signalling pathways are characterized by a cascade of multiple kinases that contribute to regulate a variety of extracellular stimuli, thereby to control the cellular environment.
The MAPK family includes the ERKs (extracellular signal-regulated kinase), the JNKs (c-Jun N-terminal kinase), the p38 MAPKs and ERK5. The ERKs generally regulate cellular proliferation and differentiation processes in response to growth factors and other hormones while the JNKs and p38 MAPKs are primarily activated in response to extracellular stresses, such as U.V. irradiation, osmotic stress or inflammatory stimuli (Biondi and Nebreda, 2003).
MAPKs are serine/threonine kinases that tend to phosphorylate their substrates on S/T-P motif. As the sequence S/T-P is found in ~ 80% of all proteins additional factors are required to direct individual kinases towards the correct substrates (Bardwell, 2006). One way by which the MAPKs ensure their substrate specificity is by interaction through docking motifs, short amino acid stretches located on MAPK-interacting proteins.
The classical docking motif is characterized by a cluster of at least two positively charged amino acids followed by by a spacer of 2-to-6 residues from a hydrophobic-X-hydrophobic sequence, where the hydrophobic residues are long-chain aliphatics (usually Leu, Ile). Both in the spacer and in the sequence immediately C-terminal to the hydrophobic-X-hydrophobic element, there is a high propensity for the presence of Pro, Asn, and/or Gly, which are residues that are both turn-forming and helix-breaking (Bardwell, 2000).
Another type of docking motif is a short peptide containing the sequence FXFP that is usually downstream of the phosphorylation site. This motif was originally found to bind the ERK subfamily but lately it has been shown to promote the interaction with p38alpha and p38 beta2 (Jacobs et al., 1999; Galanis el at., 2001).
Substrates can contain the classical docking motif or the FXFP or often contain both. (Sharrocks et al., 2000).

o Selected references

Bardwell AJ, Flatauer LJ, Matsukuma K, Thorner J, Bardwell L
A conserved docking site in MEKs mediates high-affinity binding to MAP kinases and cooperates with a scaffold protein to enhance signal transmission.
J Biol Chem 2001 Mar 30;276(13) : 10374-86.
PMID: 11134045

Bardwell L
Mechanisms of MAPK signalling specificity.
Biochem Soc Trans 2006 Nov;34() : 837-41.
PMID: 17052210

Biondi RM, Nebreda AR
Signalling specificity of Ser/Thr protein kinases through docking-site-mediated interactions.
Biochem J 2003 May 15;372() : 1-13.
PMID: 12600273

Galanis A, Yang SH, Sharrocks AD
Selective targeting of MAPKs to the ETS domain transcription factor SAP-1.
J Biol Chem 2001 Jan 12;276(2) : 965-73.
PMID: 11029469

Jacobs D, Glossip D, Xing H, Muslin AJ, Kornfeld K
Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase.
Genes Dev 1999 Jan 15;13(2) : 163-75.
PMID: 9925641

Kallunki T, Deng T, Hibi M, Karin M
c-Jun can recruit JNK to phosphorylate dimerization partners via specific docking interactions.
Cell 1996 Nov 29;87(5) : 929-39.
PMID: 8945519

Sharrocks AD, Yang SH, Galanis A
Docking domains and substrate-specificity determination for MAP kinases.
Trends Biochem Sci 2000 Sep;25(9) : 448-53.
PMID: 10973059

o This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.

Biological Process
  protein kinase cascade
  MAPKKK cascade
  activation of MAPK
Cellular Component
  nucleus
  cytosol
Molecular Function
  mitogen-activated protein kinase binding
  mitogen-activated protein kinase p38 binding

 

o Instances for LIG_MAPK_1

SequencePositionSubsequence
(Click for evidence information)
PDBGene NameProtein DescriptionOrganism
ELK1_HUMAN 312-321 ISQPQKGRKPRDLELPLSPSL - Name=ELK1; ETS domain-containing protein Elk-1. Homo sapiens (Human).
ELK4_HUMAN 318-327 VNNSSRSKKPKGLELAPTLVI - Name=ELK4; Synonyms=SAP1; ETS domain-containing protein Elk-4 (Serum response factor accessory protein 1) (SAP-1). Homo sapiens (Human).
ELK3_MOUSE 292-301 PSLPPKGKKPKGLEISAPQLL - Name=Elk3; Synonyms=Erp, Net; ETS domain-containing protein Elk-3 (ETS-related protein NET) (ETS- related protein ERP). Mus musculus (Mouse).
MP2K1_HUMAN 3-11 MPKKKPTPIQLNPAPDG - Name=MAP2K1; Synonyms=MEK1, PRKMK1; Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.12.2) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1). Homo sapiens (Human).
MP2K4_HUMAN 40-48 SSMQGKRKALKLNFANPPFK - Name=MAP2K4; Synonyms=JNKK1, MKK4, PRKMK4, SERK1; Dual specificity mitogen-activated protein kinase kinase 4 (EC 2.7.12.2) (MAP kinase kinase 4) (JNK-activating kinase 1) (c-Jun N-terminal kinase kinase 1) (JNKK) (SAPK/ERK kinase 1) (SEK1). Homo sapiens (Human).
MEF2A_HUMAN 269-277 LGMNSRKPDLRVVIPPSSKG - Name=MEF2A; Synonyms=MEF2; Myocyte-specific enhancer factor 2A (Serum response factor-like protein 1). Homo sapiens (Human).
DAPK1_HUMAN 1387-1395 LRELGRRDAADLLLKASSVF - Name=DAPK1; Synonyms=DAPK; Death-associated protein kinase 1 (EC 2.7.11.1) (DAP kinase 1). Homo sapiens (Human).
JUN_HUMAN 32-42 GYSNPKILKQSMTLNLADPVGS - Name=JUN; Transcription factor AP-1 (Activator protein 1) (AP1) (Proto-oncogene c-jun) (V-jun avian sarcoma virus 17 oncogene homolog) (p39). Homo sapiens (Human).
STE7_YEAST 9-19 RKTLQRRNLKGLNLNLHPDVGN - Name=STE7; OrderedLocusNames=YDL159W; ORFNames=D1525; Serine/threonine-protein kinase STE7 (EC 2.7.12.2). Saccharomyces cerevisiae (Baker's yeast).
STE7_YEAST 62-71 SNLFLRRGIKKKLTLDAFGDD - Name=STE7; OrderedLocusNames=YDL159W; ORFNames=D1525; Serine/threonine-protein kinase STE7 (EC 2.7.12.2). Saccharomyces cerevisiae (Baker's yeast).
MSG5_YEAST 29-38 RSLQNRNTKNLSLDIAALHPL - Name=MSG5; OrderedLocusNames=YNL053W; ORFNames=N2480, YNL2480W; Tyrosine-protein phosphatase MSG5 (EC 3.1.3.48). Saccharomyces cerevisiae (Baker's yeast).
DIG1_YEAST 97-107 PKKSLKRGRVPAPLNLSDSNTN - Name=DIG1; Synonyms=RST1; OrderedLocusNames=YPL049C; ORFNames=P7102.02; Down-regulator of invasive growth 1 (Regulator of sterile twelve 1) (Regulator of STE12 protein 1). Saccharomyces cerevisiae (Baker's yeast).
DIG2_YEAST 100-110 LNHSLKRKRVPPALNFSDIQAS - Name=DIG2; Synonyms=RST2; OrderedLocusNames=YDR480W; ORFNames=D8035.23; Down-regulator of invasive growth 2 (Regulator of sterile twelve 2) (Regulator of STE12 protein 2). Saccharomyces cerevisiae (Baker's yeast).