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Switch #:
SWTI000289
Switch type:
Specificity
Switch subtype:
Altered binding specificity

Description:
Adhesion-dependent phosphorylation of Y892 in Dystroglycan (DAG1) by c-Src (SRC) switches the specificity of DAG1 from WW domain containing proteins like Utrophin (UTRN) to SH2 domain containing proteins like Tyrosine-protein kinase CSK (CSK).

Participants:
(1) Dystroglycan (DAG1)
(2) Utrophin (UTRN)
(3) Tyrosine-protein kinase CSK (CSK)

Interactions
Interaction #1 DAG1 - UTRN

Is mutually exclusive with Interaction #2 DAG1 - CSK

Interfaces
(1) LIG_WW_1 motif (889PPPY892) in Dystroglycan (DAG1)
(2) WW domain (2815-2843) in Utrophin (UTRN)

Interaction Regulation
PTM-dependent Abrogation (Phosphorylation of Y892 on Dystroglycan (DAG1)) of the Dystroglycan (DAG1) LIG_WW_1 motif - Utrophin (UTRN) WW domain interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: Y892 : Proto-oncogene tyrosine-protein kinase Src (SRC).

Interaction #2 DAG1 - CSK

Is mutually exclusive with Interaction #1 DAG1 - UTRN

Interfaces
(3) LIG_SH2_SRC motif (892YVPP895) in Dystroglycan (DAG1)
(4) SH2 domain (82-156) in Tyrosine-protein kinase CSK (CSK)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of Y892 on Dystroglycan (DAG1)) of the Dystroglycan (DAG1) LIG_SH2_SRC motif - Tyrosine-protein kinase CSK (CSK) SH2 domain interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: Y892 : Proto-oncogene tyrosine-protein kinase Src (SRC).

Context
Switch localisation
ELM curated: cytosol, integral membrane protein, integral plasma membrane protein
Inferred: cytoplasm, cytoskeleton, plasma membrane
References

(1) Adhesion-dependent tyrosine phosphorylation of (beta)-dystroglycan regulates its interaction with utrophin.
James et al. J. Cell. Sci. (2000)

(2) Tyrosine phosphorylation of beta-dystroglycan at its WW domain binding motif, PPxY, recruits SH2 domain containing proteins.
Sotgia et al. Biochemistry (2001)

See also

Other switches involving participants
Dystroglycan (DAG1) - 3 more (view)

Other switches involving interfaces
SH2 domain - 140 more (view)
WW domain - 105 more (view)
LIG_SH2_SRC - 8 more (view)
LIG_WW_1 - 17 more (view)


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