Disease relevance of TOM1L1

• Srcasm Corrects Fyn-induced Epidermal Hyperplasia by Kinase Down-regulation [1].
• Conclusions: Increased levels of Srcasm mRNA and protein are seen in psoriasis [2].

High impact information on TOM1L1

• In vitro, increased Srcasm levels promote activation of endogenous Fyn and keratinocyte differentiation [1].
• In contrast, K14-Fyn/Srcasm-P transgenic mice, which express a nonphosphorylatable Srcasm mutant, maintained the hyperproliferative phenotype [1].
• Therefore, Srcasm is a novel regulator of Fyn promoting kinase down-regulation in a phosphorylation-dependent manner [1].
• Data presented here demonstrate that epidermal growth factor (EGF) receptor ligands promote the tyrosine phosphorylation of endogenous and adenovirally transduced Srcasm in keratinocytes, and that increased levels of Srcasm activate endogenous SFKs, with a preference for Fyn and Src [3].
• Collectively, these data demonstrate that Srcasm plays a role in linking EGF receptor- and SFK-dependent signaling to differentiation in keratinocytes [3].

Associations of TOM1L1 with chemical compounds

• In RBL-2H3 mast cells, the overexpressed TOM1L1 was strongly tyrosine phosphorylated in non-stimulated cells, and this phosphorylation was enhanced by FcepsilonRI aggregation [4].

Biological context of TOM1L1

• Tyrosine phosphorylation of Srcasm is dependent on growth factors and the activity of EGFR and SFKs [3].
• TOM1 and its related proteins, TOM1-like1 (TOM1-L1) and TOM1-like2 (TOM1-L2), constitute a subfamily of the VHS domain protein family [5].

Anatomical context of TOM1L1

• Elevated Srcasm levels inhibit keratinocyte proliferation while promoting specific aspects of keratinocyte differentiation [3].

Other interactions of TOM1L1

• We also show that a human paralog of TOM1 (TOM1-like gene 1) exists [6].
• Srcasm modulates EGF and Src-kinase signaling in keratinocytes [3].
• Increased Srcasm expression enhances p44/42 mitogen-activated protein kinase activity and Elk-1-dependent transcriptional events [3].

Analytical, diagnostic and therapeutic context of TOM1L1

• Northern blot analysis of murine tissues demonstrates that Srcasm expression is highest in brain and kidney [7].
• In situ hybridization analysis reveals that srcasm mRNA is expressed in regions of the epidermis and hair follicle where keratinocyte differentiation occurs [7].
• Expression of Srcasm protein was evaluated by protein immunohistochemistry and Western blotting of protein lysates derived from patient samples [2].
• Methods: The levels of Srcasm mRNA were determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) on RNA isolated from unremarkable and lesional patient tissue [2].

References