TC21 regulation pathway
Related RAS viral (r-ras) oncogene homolog 2 (TC21)
belongs to Ras family of small GTPases. It plays pivotal role in cell growth and
differentiation , .
Guanine nucleotide exchange factors (GEFs), which promote GTP loading on
TC21 are essential for TC21
activation and GTPase activating proteins (GAPs), which stimulate hydrolysis of GTP to
GDP, negatively regulates TC21 activity .
Main GEFs for TC21 are RAS guanyl releasing proteins 1, 2
and 3 (CALDAG-GEFII,
that can be activated by increased Ca(2'+) cytosol and
DAG levels , ; Ras
protein-specific guanine nucleotide-releasing factor 1
(RASGRF1) that is activated by Lymphocyte-specific protein
tyrosine kinase (Lck) phosphorylation , , ; and Rap guanine nucleotide exchange factor (GEF) 1
(C3G) that is stimulated by Growth factor receptor-bound
protein 2 (GRB2) binding , .
Known GEF for TC21 is RAS p21 protein activator 1
(p120GAP) , . Breakpoint
cluster region (BCR) via Docking protein 1 and 2
(DOK1, DOK2) phosphorylation
stimulates GAP activity of p120GAP , . V-src sarcoma (c-Src) phosphorylation and RAP1A,
member of RAS oncogene family (RAP-1A) binding suppress GAP
activity of p120GAP , . RAS
p21 protein activator 2 (RASA2), activated by
Inositol 1,3,4,5-tetrakisphosphate cytosol binding or
G-protein alpha-12 family signaling, also exhibits GAP
activity towards TC21 , , . Another known TC21 GAP is Neurofibromin 1
(Neurofibromin) , .
GTP-bound TC21 can stimulate the Raf kinase family
members v-raf-1 murine leukemia viral oncogene homolog 1 (c-Raf-1)
and v-raf murine sarcoma viral oncogene
homolog B1 (B-raf) and thus promote
activation of Mitogen-activated protein kinases 1 and 3
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