Oncostatin-M is a cytokine produced by activated lymphoid cells that regulates the proliferation of a number of tumour cell lines. It may play a role in the pathogenesis of AIDS-KS [].
This region is found in the transcription factor Aft1 which is required for a wide range of stress responses. The OSM domain has been shown to be involved in the osmotic stress response [].
On the basis of functional and structural similarities, the small cytokines leukemia inhibitory factor (LIF) and oncostatin (OSM) can be classified into a single family [, ].It has been said []that LIF and OSM can be included in the IL-6 family of cytokines, but while all these cytokines seem to be structurally related, the sequence similarity is not high enough to allow the use of a single consensus pattern.
On the basis of functional and structural similarities, the small cytokines leukemia inhibitory factor (LIF) and oncostatin (OSM) can be classified into a single family [, ].It has been said []that LIF and OSM can be included in the IL-6 family of cytokines, but while all these cytokines seem to be structurally related, the sequence similarity is not high enough to allow the use of a single consensus pattern.The signature pattern for this entry is based on a conserved region in the C-terminal region. This region is centred on a conserved cysteine which has been shown, in OSM, to be involved in a disulphide bond [].
This is the D2 domain in cytokine-binding module 1 (CBM1) found in Leukemia inhibitory factor receptor (LIFR) and OSM receptors (OSMR). LIFR has an extracellular region with a modular structure containing two cytokine-binding modules (CBM) separated by an Ig-like domain and followed by three membrane-proximal fibronectin type-III (FNIII) domains. The D2 domain in CBM1 shows structural similarity to the corresponding CBM domains of both gp130 and IL-6Ralpha because it contains conserved structural features like the WSXWS motif [, ]. The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation [].
Programmed cell death 10 protein (PDCD10/CCM3) is part of the CCM complex and is required for neuronal migration []. It also has roles outside of this complex [], it is crucial in vascularization and in angiogenesis as it functions in vessel permeability and stability []. PDCD10/CCM3 was originally discovered to be upregulated during granulocyte apoptosis and is thought to play a role in cell death []. However, a specific role for PDCD10 in cell survival is not clear as both pro-survival and pro-apoptotic effects have been reported [, ]. PDCD10/CCM3 contains an N-terminal dimerisation domain and a C-terminal focal adhesion targeting-homology (FAT-H) domain [].There are three CCM proteins: CCM1 (also known as KRIT1), CCM2 (also known as OSM and malcavernin) and CCM3 (also known as PDCD10). Mutations in the genes encoding CCM proteins cause cerebral cavernous malformations (CCMs), a disease characterised by dilated leaky blood vessels, especially in the neurovasculature, that result in increased risk of stroke, focal neurological defects and seizures. The CCM proteins can form a trimeric complex. They can also interact with a range of signaling, cytoskeletal and adaptor proteins that may account for their roles in a range of basic cellular processes including cell adhesion, migration, polarity and apoptosis [].
