D
IPR035750

Fyn/Yrk, SH3 domain

InterPro entry
Short nameFyn/Yrk_SH3
Overlapping
homologous
superfamilies
 
domain relationships

Description

Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn is involved in the control of cell growth and is required in diverse pathways, including T and B cell receptor signalling, integrin-mediated signalling, growth factor and cytokine receptor signalling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilisation, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells
[2]
. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's
[4]
and Parkinson's diseases
[6]
. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury
[5]
.

Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction
[3, 1]
.

References

1.Structure and dynamic regulation of Src-family kinases. Engen JR, Wales TE, Hochrein JM, Meyn MA 3rd, Banu Ozkan S, Bahar I, Smithgall TE. Cell. Mol. Life Sci. 65, 3058-73, (2008). View articlePMID: 18563293

2.Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. Palacios EH, Weiss A. Oncogene 23, 7990-8000, (2004). View articlePMID: 15489916

3.Src family kinases: regulation of their activities, levels and identification of new pathways. Ingley E. Biochim. Biophys. Acta 1784, 56-65, (2008). View articlePMID: 17905674

4.Regulatory region genetic variation is associated with FYN expression in Alzheimer's disease. Zahratka JA, Shao Y, Shaw M, Todd K, Formica SV, Khrestian M, Montine T, Leverenz JB, Bekris LM. Neurobiol. Aging 51, 43-53, (2017). View articlePMID: 28033507

5.Tissue specific expression of Yrk kinase: implications for differentiation and inflammation. Martins-Green M, Bixby JL, Yamamoto T, Graf T, Sudol M. Int. J. Biochem. Cell Biol. 32, 351-64, (2000). View articlePMID: 10716632

6.Fyn Kinase Regulates Microglial Neuroinflammatory Responses in Cell Culture and Animal Models of Parkinson's Disease. Panicker N, Saminathan H, Jin H, Neal M, Harischandra DS, Gordon R, Kanthasamy K, Lawana V, Sarkar S, Luo J, Anantharam V, Kanthasamy AG, Kanthasamy A. J. Neurosci. 35, 10058-77, (2015). View articlePMID: 26157004

Cross References

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